Rational design of alpha-helical antifreeze peptides.

The alanine-rich alpha-helical antifreeze protein from the winter flounder Pseudopleuronectes americanus adsorbs to specific planes of ice guided by an ice lattice match to threonine residues regularly spaced 16.6 A apart. We report here that by redesigning the winter flounder antifreeze peptide to incorporate a 27.1-A spacing between putative 'ice-binding' threonines, the deduced binding alignment of the helical molecule on the ice lattice is changed from the Miller indices directional vector [1102 ] to [2203 ]. Subsequent ice-binding characteristics are altered, including changes in adsorption specificity, decreases in thermal hysteresis activity and the formation of rotated hexagonal bipyramid ice crystal morphology.     

Energy-optimized structure of antifreeze protein and its binding mechanism.

A combination of Monte Carlo simulated annealing and energy minimization was utilized to determine the conformation of the antifreeze protein from the fish winter flounder. It was found from the energy-optimized structure that the hydroxyl groups of its four threonine residues, i.e. Thr2, Thr13, Thr24, Thr35, are aligned on almost the same line parallel to the helix axis and separated successively by 16.1, 16.0 and 16.2 A, respectively, very close to the 16.6 A repeat spacing along [0112] in ice. Based on such a space match, a zipper-like model is proposed to elucidate the binding mechanism of the antifreeze protein to ice crystals. According to the current model, the antifreeze protein may bind to an ice nucleation structure in a zipper-like fashion through hydrogen bonding of the hydroxyl groups of these four Thr residues to the oxygen atoms along the [0112] direction in ice lattice, subsequently stopping or retarding the growth of ice pyramidal planes so as to depress the freeze point. The calculated results and the binding mechanism thus derived accord with recent experimental observations. The mechanistic implications derived from such a special antifreeze molecule might be generally applied to elucidate the structure-function relationship of other antifreeze proteins with the following two common features: (1) recurrence of a Thr residue (or any other polar amino acid residue whose side-chain can form a hydrogen bond with water) in an 11-amino-acid period along the sequence concerned; and (2) a high percentage of Ala residue component therein. Further experiments are suggested to test the ice binding model.     

Adsorption to ice of fish antifreeze glycopeptides 7 and 8.

Experimental results show that fish antifreeze glycopeptides (AFGPs) 8 and 7 (with 4 and 5 repeats respectively of the Ala-Ala-Thr backbone sequence) bond onto ice prism planes aligned along a-axes, and inhibit crystal growth on prism planes and on surfaces close to that orientation. The 9.31-A repeat spacing of the AFGP in the polyproline II helix configuration, deduced from NMR studies, matches twice the repeat spacing of ice in the deduced alignment direction, 9.038 A, within 3%. A specific binding model is proposed for the AFGP and for the alpha-helical antifreeze peptide of winter flounder. For AFGP 7-8, two hydroxyl groups of each disaccharide (one disaccharide is attached to each threonine) reside within the ice surface, so that they are shared between the ice crystal and the disaccharide. This provides 24 hydrogen bonds between AFGP 8 and the ice and 30 for AFGP 7, explaining why the chemical adsorption is virtually irreversible and the crystal growth can be stopped virtually completely. The same scheme of sharing polar groups with the ice works well with the alpha-helical antifreeze of winter flounder, for which an amide as well as several hydroxyls are shared. The sharing of polar groups with the ice crystal, rather than hydrogen-bonding to the ice surface, may be a general requirement for adsoprtion-inhibition of freezing.     

Effect of chain topology on the self-organization and dynamics of block copolypeptides: from diblock copolymers to stars

The effect of chain topology on (i) the peptide secondary structure, (ii) the nanophase self-assembly, and (iii) the local segmental and global peptide relaxations has been studied in a series of model diblock and 3-arm star copolypeptides of poly(epsilon-carbobenzyloxy-L-lysine) (PZLL) and poly(gamma-benzyl-L-glutamate) (PBLG) with PZLL forming the core. Diblock copolypeptides are nanophase separated with PBLG and PZLL domains comprising alpha-helices packed in a hexagonal lattice. Star copolypeptides are only weakly phase separated, comprising PBLG and PZLL alpha-helices in a pseudohexagonal lattice. Phase mixing has profound consequences on the local and global dynamics. The relaxation of the peptide secondary structure speeds up, and the helix persistence length is further reduced in the stars, signifying an increased concentration of helical defects.     

Type I 'antifreeze' proteins. Structure-activity studies and mechanisms of ice growth inhibition.

The type I 'antifreeze' proteins, found in the body fluids of fish inhabiting polar oceans, are alanine-rich alpha-helical proteins that are able to inhibit the growth of ice. Within this class there are two distinct subclasses of proteins: those related to the winter flounder sequence HPLC6 and which contain 11-residue repeat units commencing with threonine; and those from the sculpins that are unique in the N-terminal region that contains established helix breakers and lacks the 11-residue repeat structure present in the rest of the protein. Although 14 type I proteins have been isolated, almost all research has focused on HPLC6, the 37-residue protein from the winter flounder Pseudopleuronectes americanus. This protein modifies both the rate and shape (or 'habit') of ice crystal growth, displays hysteresis and accumulates specifically at the {2 0 2; 1} ice plane. Until very recently, all models to explain the mechanism for this specific interaction have relied on the interaction of the four threonine hydroxyls, which are spaced equally apart on one face of the helix, with the ice lattice. In contrast, proteins belonging to the sculpin family accumulate specifically at the {2 1; 1; 0} plane. The molecular origin of this difference in specificity between the flounder and sculpin proteins is not understood. This review will summarize the structure-activity and molecular modelling and dynamics studies on HPLC6, with an emphasis on recent studies in which the threonine residues have been mutated. These studies have identified important hydrophobic contributions to the ice growth inhibition mechanism. Some 50 mutants of HPLC6 have been reported and the data is consistent with the following requirements for ice growth inhibition: (a) a minimum length of approx. 25 residues; (b) an alanine-rich sequence in order to induce a highly helical conformation; (c) a hydrophobic face; (d) a number of charged/polar residues which are involved in solubility and/or interaction with the ice surface. The emerging picture, that requires further dynamics studies including accurate modelling of the ice/water interface, suggests that a hydrophobic interaction between the surface of the protein and ice is the key to explaining accumulation at specific ice planes, and thus the molecular level mechanism for ice growth inhibition.     

Increasing nest predation will be insufficient to maintain polar bear body condition in the face of sea ice loss

Climate change can influence interspecific interactions by differentially affecting species‐specific phenology. In seasonal ice environments, there is evidence that polar bear predation of Arctic bird eggs is increasing because of earlier sea ice breakup, which forces polar bears into nearshore terrestrial environments where Arctic birds are nesting. Because polar bears can consume a large number of nests before becoming satiated, and because they can swim between island colonies, they could have dramatic influences on seabird and sea duck reproductive success. However, it is unclear whether nest foraging can provide an energetic benefit to polar bear populations, especially given the capacity of bird populations to redistribute in response to increasing predation pressure. In this study, we develop a spatially explicit agent‐based model of the predator–prey relationship between polar bears and common eiders, a common and culturally important bird species for northern peoples. Our model is composed of two types of agents (polar bear agents and common eider hen agents) whose movements and decision heuristics are based on species‐specific bioenergetic and behavioral ecological principles, and are influenced by historical and extrapolated sea ice conditions. Our model reproduces empirical findings that polar bear predation of bird nests is increasing and predicts an accelerating relationship between advancing ice breakup dates and the number of nests depredated. Despite increases in nest predation, our model predicts that polar bear body condition during the ice‐free period will continue to decline. Finally, our model predicts that common eider nests will become more dispersed and will move closer to the mainland in response to increasing predation, possibly increasing their exposure to land‐based predators and influencing the livelihood of local people that collect eider eggs and down. These results show that predator–prey interactions can have nonlinear responses to changes in climate and provides important predictions of ecological change in Arctic ecosystems.     

Artificial antifreeze polypeptides: alpha-helical peptides with KAAK motifs have antifreeze and ice crystal morphology modifying properties.

Antifreeze polypeptides from fish are generally thought to inhibit ice crystal growth by specific adsorption onto ice surfaces and preventing addition of water molecules to the ice lattice. Recent studies have suggested that this adsorption results from hydrogen bonding through the side chains of polar amino acids as well as hydrophobic interactions between the non-polar domains on the ice-binding side of antifreeze polypeptides and the clathrate-like surfaces of ice. In order to better understand the activity of one of the antifreeze polypeptide families, namely the alpha-helical type I antifreeze polypeptides, four alpha-helical peptides having sequences not directly analogous to those of known antifreeze polypeptides and containing only positively charged and non-polar side chains were synthesized. Two peptides with regularly spaced lysine residues, GAAKAAKAAAAAAAKAAKAAAAAAAKAAKAAGGY-NH2 and GAALKAAKAAAAAALKAAKAAAAAALKAAKAAGGY-NH2, showed antifreeze activity, albeit weaker than seen in natural antifreeze polypeptides, by the criteria of freezing point depression (thermal hysteresis) and ice crystal modification to a hexagonal trapezohedron. Peptides with irregular spacing of Lys residues were completely inactive. Up to now, lysine residues have not been generally associated with antifreeze activity, though they have been implicated in some antifreeze polypeptides. This work also shows that lysine residues in themselves, when properly positioned on an alpha-helical polyalanine scaffold, have all the requisite properties needed for such an activity.     

Consequences of long-distance swimming and travel over deep-water pack ice for a female polar bear during a year of extreme sea ice retreat

Polar bears (Ursus maritimus) prefer to live on Arctic sea ice but may swim between ice floes or between sea ice and land. Although anecdotal observations suggest that polar bears are capable of swimming long distances, no data have been available to describe in detail long distance swimming events or the physiological and reproductive consequences of such behavior. Between an initial capture in late August and a recapture in late October 2008, a radio-collared adult female polar bear in the Beaufort Sea made a continuous swim of 687 km over 9 days and then intermittently swam and walked on the sea ice surface an additional 1,800 km. Measures of movement rate, hourly activity, and subcutaneous and external temperature revealed distinct profiles of swimming and walking. Between captures, this polar bear lost 22% of her body mass and her yearling cub. The extraordinary long distance swimming ability of polar bears, which we confirm here, may help them cope with reduced Arctic sea ice. Our observation, however, indicates that long distance swimming in Arctic waters, and travel over deep water pack ice, may result in high energetic costs and compromise reproductive fitness.     

Increased Arctic sea ice drift alters adult female polar bear movements and energetics

Recent reductions in thickness and extent have increased drift rates of Arctic sea ice. Increased ice drift could significantly affect the movements and the energy balance of polar bears (Ursus maritimus) which forage, nearly exclusively, on this substrate. We used radio‐tracking and ice drift data to quantify the influence of increased drift on bear movements, and we modeled the consequences for energy demands of adult females in the Beaufort and Chukchi seas during two periods with different sea ice characteristics. Westward and northward drift of the sea ice used by polar bears in both regions increased between 1987–1998 and 1999–2013. To remain within their home ranges, polar bears responded to the higher westward ice drift with greater eastward movements, while their movements north in the spring and south in fall were frequently aided by ice motion. To compensate for more rapid westward ice drift in recent years, polar bears covered greater daily distances either by increasing their time spent active (7.6%–9.6%) or by increasing their travel speed (8.5%–8.9%). This increased their calculated annual energy expenditure by 1.8%–3.6% (depending on region and reproductive status), a cost that could be met by capturing an additional 1–3 seals/year. Polar bears selected similar habitats in both periods, indicating that faster drift did not alter habitat preferences. Compounding reduced foraging opportunities that result from habitat loss; changes in ice drift, and associated activity increases, likely exacerbate the physiological stress experienced by polar bears in a warming Arctic.     

Effects of Earlier Sea Ice Breakup on Survival and Population Size of Polar Bears in Western Hudson Bay

ABSTRACT Some of the most pronounced ecological responses to climatic warming are expected to occur in polar marine regions, where temperature increases have been the greatest and sea ice provides a sensitive mechanism by which climatic conditions affect sympagic (i.e., with ice) species. Population-level effects of climatic change, however, remain difficult to quantify. We used a flexible extension of Cormack-Jolly-Seber capture-recapture models to estimate population size and survival for polar bears (Ursus maritimus), one of the most ice-dependent of Arctic marine mammals. We analyzed data for polar bears captured from 1984 to 2004 along the western coast of Hudson Bay and in the community of Churchill, Manitoba, Canada. The Western Hudson Bay polar bear population declined from 1,194 (95% CI = 1,020-1,368) in 1987 to 935 (95% CI = 794-1,076) in 2004. Total apparent survival of prime-adult polar bears (5–19 yr) was stable for females (0.93; 95% CI = 0.91-0.94) and males (0.90; 95% CI = 0.88-0.91). Survival of juvenile, subadult, and senescent-adult polar bears was correlated with spring sea ice breakup date, which was variable among years and occurred approximately 3 weeks earlier in 2004 than in 1984. We propose that this correlation provides evidence for a causal association between earlier sea ice breakup (due to climatic warming) and decreased polar bear survival. It may also explain why Churchill, like other communities along the western coast of Hudson Bay, has experienced an increase in human-polar bear interactions in recent years. Earlier sea ice breakup may have resulted in a larger number of nutritionally stressed polar bears, which are encroaching on human habitations in search of supplemental food. Because western Hudson Bay is near the southern limit of the species' range, our findings may foreshadow the demographic responses and management challenges that more northerly polar bear populations will experience if climatic warming in the Arctic continues as projected.     

Light‐driven tipping points in polar ecosystems

Some ecosystems can undergo abrupt transformation in response to relatively small environmental change. Identifying imminent ‘tipping points’ is crucial for biodiversity conservation, particularly in the face of climate change. Here, we describe a tipping point mechanism likely to induce widespread regime shifts in polar ecosystems. Seasonal snow and ice‐cover periodically block sunlight reaching polar ecosystems, but the effect of this on annual light depends critically on the timing of cover within the annual solar cycle. At high latitudes, sunlight is strongly seasonal, and ice‐free days around the summer solstice receive orders of magnitude more light than those in winter. Early melt that brings the date of ice‐loss closer to midsummer will cause an exponential increase in the amount of sunlight reaching some ecosystems per year. This is likely to drive ecological tipping points in which primary producers (plants and algae) flourish and out‐compete dark‐adapted communities. We demonstrate this principle on Antarctic shallow seabed ecosystems, which our data suggest are sensitive to small changes in the timing of sea‐ice loss. Algae respond to light thresholds that are easily exceeded by a slight reduction in sea‐ice duration. Earlier sea‐ice loss is likely to cause extensive regime shifts in which endemic shallow‐water invertebrate communities are replaced by algae, reducing coastal biodiversity and fundamentally changing ecosystem functioning. Modeling shows that recent changes in ice and snow cover have already transformed annual light budgets in large areas of the Arctic and Antarctic, and both aquatic and terrestrial ecosystems are likely to experience further significant change in light. The interaction between ice‐loss and solar irradiance renders polar ecosystems acutely vulnerable to abrupt ecosystem change, as light‐driven tipping points are readily breached by relatively slight shifts in the timing of snow and ice‐loss.     

Adsorption of alpha-helical antifreeze peptides on specific ice crystal surface planes.

The noncolligative peptide and glycopeptide antifreezes found in some cold-water fish act by binding to the ice surface and preventing crystal growth, not by altering the equilibrium freezing point of the water. A simple crystal growth and etching technique allows determination of the crystallographic planes where the binding occurs. In the case of elongated molecules, such as the alpha-helical peptides in this report, it also allows a deduction of the molecular alignment on the ice surface. The structurally similar antifreeze peptides from winter flounder (Pseudopleuronectes americanus) and Alaskan plaice (Pleuronectes quadritaberulatus) adsorb onto the (2021) pyramidal planes of ice, whereas the sculpin (Myoxocephalus scorpius) peptide adsorbs on (2110), the secondary prism planes. All three are probably aligned along (0112). These antifreeze peptides have 11-amino acid sequence repeats ending with a polar residue, and each repeat constitutes a distance of 16.5 A along the helix, which nearly matches the 16.7 A repeat spacing along (0112) in ice. This structural match is undoubtedly important, but the mechanism of binding is not yet clear. The suggested mechanism of growth inhibition operates through the influence of local surface curvature upon melting point and results in complete inhibition of the crystal growth even though individual antifreeze molecules bind at only one interface orientation.     

A series of lysyldipeptide derivatives for racemization studies in peptide synthesis.

The series of diastereomeric peptide derivatives N-benzoyl-D,L-X-N epsilon-benzyloxycarbonyl-L-lysine methyl ester where X = alanyl, valyl, leucyl, phenylalanyl and isoleucyl are submitted as model systems for studying racemization in peptide synthesis. The diastereomers can be analyzed by quantitation of the separated ester methyl proton peaks of their nuclear magnetic resonance spectra. Data on the tendency to racemize of the different residues are presented. In polar solvents, valyl and isoleucyl residues racemize more readily than the other residues.     

Are polar bear habitat resource selection functions developed from 1985–1995 data still useful?

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High resolution structure of an oligomeric eye lens beta-crystallin. Loops, arches, linkers and interfaces in beta B2 dimer compared to a monomeric gamma-crystallin.

beta-Crystallins are polydisperse, oligomeric structural proteins that have a major role in forming the high refractive index of the eye lens. Using single crystal X-ray crystallography with molecular replacement, the structure of beta B2 dimer has been solved at 2.1 A resolution. Each subunit comprises an N and C-terminal domain that are very similar and each domain is formed from two similar "Greek key" motifs related by a local dyad. Sequence differences in the internally quadruplicated molecules, analysed in terms of their beta-sheets, hairpins and arches, give rise to structural differences in the motifs. Whereas the related family of gamma-crystallins are monomers, beta-crystallins are always oligomers. In the beta B2 subunit, the domains, each comprising two motifs, are separated by an extended linking peptide. A crystallographic 2-fold axis relates the two subunits of the dimer so that the N-terminal domain of one subunit of beta B2 and the C-terminal domain of the symmetry-related subunit are topologically equivalent to the two covalently connected domains of gamma B-crystallin. The intersubunit domain interface is very similar to the intradomain interface of gamma B, although many sequence differences have resulted in an increase in polar interactions between domains in beta B2. Comparison of the structures of beta B2 and gamma B-crystallins shows that the two families differ largely in the conformation of their connecting peptides. A further extensive lattice contact indicates a tetramer with 222 symmetry. The ways in which insertions and extensions in the beta-crystallin effect oligomer interactions are described. The two kinds of crystallin are analysed for structural features that account for their different stabilities. These studies are a basis for understanding formation of higher aggregates in the lens.     

Alternative roles for putative ice-binding residues in type I antifreeze protein

Two sets of variants of type I antifreeze protein have been synthesized to investigate the role of Leu and Asn in the activity of this 37-residue alpha-helix. Leu and Asn flank the central two of four regularly spaced ice-binding Thr in the i-1 and i + 3 positions, respectively. All three residues project from the same side of the helix to form the protein's putative ice-adsorption site and are considered in some models to act together as an "ice-binding motif". Replacement of Asn by residues with shorter side chains resulted in either a small loss (Ala) or gain (Thr) of antifreeze activity. However, substitution of Asn by its slightly larger homologue (Gln) abolished thermal hysteresis activity. The Gln-containing peptide was very soluble, largely monomeric, and fully helical. Of the three variants in which Leu was replaced by Ala, two of the three were more active than their Leu-containing counterparts, but all three variants began to precipitate as the peptide concentration increased. None of the seven variants tested showed dramatic differences in ice crystal morphology from that established by the wild type. These results are consistent with a primary role for Leu in preventing peptide aggregation at the antifreeze protein concentrations (10 mg/mL) normally present in fish serum. Similarly the role for Asn may have more to do with enhancing the solubility of these rather hydrophobic peptides than of making a stereospecific hydrogen-bonding match to the ice lattice as traditionally thought. Nevertheless, the dramatic loss of activity in the Asn-to-Gln replacement demonstrates the steric restriction on residues in or near the ice-binding site of the peptide.     

The stress of Arctic warming on polar bears

Arctic ecosystems are changing rapidly in response to climate warming. While Arctic mammals are highly evolved to these extreme environments, particularly with respect to their stress axis, some species may have limited capacity to adapt to this change. We examined changes in key components of the stress axis (cortisol and its carrier protein—corticosteroid binding globulin [CBG]) in polar bears (Ursus maritimus) from western Hudson Bay (N = 300) over a 33 year period (1983–2015) during which time the ice‐free period was increasing. Changing sea ice phenology limits spring hunting opportunities and extends the period of onshore fasting. We assessed the response of polar bears to a standardized stressor (helicopter pursuit, darting, and immobilization) during their onshore fasting period (late summer–autumn) and quantified the serum levels of the maximum corticosteroid binding capacity (MCBC) of CBG, the serum protein that binds cortisol strongly, and free cortisol (FC). We quantified bear condition (age, sex, female with cubs or not, fat condition), sea ice (breakup in spring–summer, 1 year lagged freeze‐up in autumn), and duration of fasting until sample collection as well as cumulative impacts of the latter environmental traits from the previous year. Data were separated into “good” years (1983–1990) when conditions were thought to be optimal and “poor” years (1991–2015) when sea ice conditions deteriorated and fasting on land was extended. MCBC explained 39.4% of the variation in the good years, but only 28.1% in the poor ones, using both biological and environmental variables. MCBC levels decreased with age. Changes in FC were complex, but more poorly explained. Counterintuitively, MCBC levels increased with increased time onshore, 1 year lag effects, and in poor ice years. We conclude that MCBC is a biomarker of stress in polar bears and that the changes we document are a consequence of climate warming.     

Spring fasting behavior in a marine apex predator provides an index of ecosystem productivity

The effects of declining Arctic sea ice on local ecosystem productivity are not well understood but have been shown to vary inter‐specifically, spatially, and temporally. Because marine mammals occupy upper trophic levels in Arctic food webs, they may be useful indicators for understanding variation in ecosystem productivity. Polar bears (Ursus maritimus) are apex predators that primarily consume benthic and pelagic‐feeding ice‐associated seals. As such, their productivity integrates sea ice conditions and the ecosystem supporting them. Declining sea ice availability has been linked to negative population effects for polar bears but does not fully explain observed population changes. We examined relationships between spring foraging success of polar bears and sea ice conditions, prey productivity, and general patterns of ecosystem productivity in the Beaufort and Chukchi Seas (CSs). Fasting status (≥7 days) was estimated using serum urea and creatinine levels of 1,448 samples collected from 1,177 adult and subadult bears across three subpopulations. Fasting increased in the Beaufort Sea between 1983–1999 and 2000–2016 and was related to an index of ringed seal body condition. This change was concurrent with declines in body condition of polar bears and observed changes in the diet, condition and/or reproduction of four other vertebrate consumers within the food chain. In contrast, fasting declined in CS polar bears between periods and was less common than in the two Beaufort Sea subpopulations consistent with studies demonstrating higher primary productivity and maintenance or improved body condition in polar bears, ringed seals, and bearded seals despite recent sea ice loss in this region. Consistency between regional and temporal variation in spring polar bear fasting and food web productivity suggests that polar bears may be a useful indicator species. Furthermore, our results suggest that spatial and temporal ecological variation is important in affecting upper trophic‐level productivity in these marine ecosystems.     

Hydrophobic binding domains of rat intestinal maltase-glucoamylase

Rat intestinal microvillus maltase-glucoamylase was isolated by detergent extraction and purification in the presence of protease inhibitors as previously described and incorporated into phospholipid vesicles. After purification of the vesicles on Sephadex G-50, maltase was labelled with 3-trifluoromethyl-3-(m-[125I]iodophenyl) diazirine ([125I]TID) by photolysis using a water-jacketed mercury vapour lamp with a saturated CuSO4 filter. The labelled enzyme was extracted with acetone, resuspended in 1% Triton X-100, reincorporated into phospholipid vesicles, and digested with activated papain to release the hydrophilic polar head of the enzyme from the vesicle bilayer. Vesicle-bound and free enzyme components were separated on Sepharose 4B. Ninety percent of the enzymatic activity was free, while a similar percentage of radioactive label remained with the vesicles in keeping with the separation of an active polar headpiece from a labelled apolar peptide in the lipid bilayer. The vesicle fractions were subjected to chromatography on Sephadex LH-60 with ethanol--formic acid (7:3) as the eluant. A single radioactive peak (14 kilodaltons (kDa)) was separated from labelled lipid. Sodium dodecyl sulfate--polyacrylamide gel electrophoresis of the peak showed a radioactive doublet of 26-28 kDa, possibly representing a dimer. No other labelled peptides were found. These results suggest that detergent-solubilized maltase-glucoamylase is inserted into the phospholipid bilayer via an apolar peptide with a minimum molecular mass of 14 kDa. The peptide probably represents a terminal anchor segment of the 145-kDa subunit which is converted to 130 kDa when the membrane-bound enzyme is solubilized by papain.     

Can the topological distribution of membrane spanning amino acid residues be responsible for the recognition of signal peptides by signal peptide peptidases?

Signal peptides are selectively recognized and degraded by membrane associated proteases called as signal peptide peptidases. The hydrolysis of the signal peptide occurs only after its cleavage from the precursor. The possible reasons for this selectivity have been investigated. The results indicate that in signal peptides, leucine residues are clustered to a large extent on the same side of the membrane spanning alpha helix as the polar residues, but are distinctly separated along the length of the axis. Such topological differences in the distribution of amino acids on the surface of the membrane spanning alpha helix may play a crucial role in selective degradation of signal peptides.