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101.
Ayman W. El-Hattab Teresa A. Smolarek Martha E. Walker Elizabeth K. Schorry LaDonna L. Immken Gayle Patel Mary-Alice Abbott Brendan C. Lanpher Zhishuo Ou Sung-Hae L. Kang Ankita Patel Fernando Scaglia James R. Lupski Sau Wai Cheung Pawel Stankiewicz 《Human genetics》2009,126(4):589-602
We report four new patients with a submicroscopic deletion in 15q24 manifesting developmental delay, short stature, hypotonia, digital abnormalities, joint laxity, genital abnormalities, and characteristic facial features. These clinical features are shared with six recently reported patients with a 15q24 microdeletion, supporting the notion that this is a recognizable syndrome. We describe a case of an ~2.6 Mb microduplication involving a portion of the minimal deletion critical region in a 15-year-old male with short stature, mild mental retardation, attention deficit hyperactivity disorder, Asperger syndrome, decreased joint mobility, digital abnormalities, and characteristic facial features. Some of these features are shared with a recently reported case with a 15q24 microduplication involving the minimal deletion critical region. We also report two siblings and their mother with duplication adjacent and distal to this region exhibiting mild developmental delay, hypotonia, tapering fingers, characteristic facial features, and prominent ears. The deletion and duplication breakpoints were mapped by array comparative genomic hybridization and the genomic structure in 15q24 was analyzed further. Surprisingly, in addition to the previously recognized three low-copy repeat clusters (BP1, BP2, and BP3), we identified two other paralogous low-copy repeat clusters that likely mediated the formation of alternative sized 15q24 genomic rearrangements via non-allelic homologous recombination. 相似文献
102.
The mechanism of oligomerization and its role in the regulation of activity in large GTPases are not clearly understood. Human guanylate binding proteins (hGBP-1 and 2) belonging to large GTPases have the unique feature of hydrolyzing GTP to a mixture of GDP and GMP with unequal ratios. Using a series of truncated and mutant proteins of hGBP-1, we identified a hydrophobic helix in the connecting region between the two domains that plays a critical role in dimerization and regulation of the GTPase activity. The fluorescence with 1-8-anilinonaphthalene sulfonate and circular dichroism measurements together suggest that in the absence of the substrate analog, the helix is masked inside the protein but becomes exposed through a substrate-induced conformational switch, and thus mediates dimerization. This is further supported by the intrinsic fluorescence experiment, where Leu298 of this helix is replaced by a tryptophan. Remarkably, the enzyme exhibits differential GTPase activities depending on dimerization; a monomer produces only GDP, but a dimer gives both GDP and GMP with stimulation of the activity. An absolute dependence of GMP formation with dimerization demonstrates a cross talk between the monomers during the second hydrolysis. Similar to hGBP-1, hGBP-2 showed dimerization-related GTPase activity for GMP formation, indicating that this family of proteins follows a broadly similar mechanism for GTP hydrolysis. 相似文献
103.
Sujay Rakshit Zerka Rashid J. C. Sekhar T. Fatma Sain Dass 《Plant Cell, Tissue and Organ Culture》2010,100(1):31-37
Callus induction and regeneration ability of five elite maize inbred lines, CM 111, CM 117, CM 124, CM 125 and CM 300 were
investigated using 14-day-old immature embryos as explants. Genotype, medium, source of auxin and their concentrations influenced
induction of callus. Explants grown on Murashige and Skoog (MS) medium supplemented with 2,4-dichlorophenoxyacetic acid at
1 mg l−1 showed the highest frequency of callusing. Among all the media tested, explants grown on N6 medium gave the highest frequency
of organogenic callus. Moreover, N6 supplemented with Dicamba promoted higher callus response in terms of both frequency of
induction as well as quality, compared to N6 medium with 2,4-D. N6 supplemented with 2 mg l−1 Dicamba induced the highest frequency of organogenic callus. Among the five genotypes tested, CM 124, CM 125, and CM 300
gave the best callus. Explants of both CM 124 and CM 300 incubated on MS medium supplemented with 1 mg l−1 benzyladenine and 0.5 mg l−1 indole acetic acid promoted the highest frequency of shoot induction. Though CM 124 induced higher percentage of shoot formation
than CM 300, the mean number of developed shoots per explant was higher for CM 300. The highest frequency of root formation
was observed when shoots were grown on MS medium supplemented with 2 mg l−1 naphathalene acetic acid. Percentage of regenerated plants ranged from 54 to 66. 相似文献
104.
Arginase is a binuclear Mn(2+)-metalloenzyme of urea cycle that catalyzes the conversion of L-arginine to L-ornithine and urea. Unlike other arginases, the Helicobacter pylori enzyme is selective for Co(2+), and has lower catalytic activity. To understand the differences in the biochemical properties as well as activity compared to other arginases, we carried out a detailed investigation of different metal reconstituted H. pylori arginases that includes steady-state kinetics, fluorescence measurement, pH-dependent and oligomerization assays. Unlike other arginases (except human at physiological pH), the Co(2+)- and Mn(2+)-reconstituted H. pylori enzymes exhibit cooperative mechanism of arginine hydrolysis, and undergo self-association and activation with increasing concentrations. Analytical gel-filtration assays in conjunction with the kinetic data showed that the protein exists as a mixture of monomer and dimer with monomer being the major form (other arginases exclusively exist as a trimer or hexamer) but the dimer is associated with higher catalytic activity. The proportion of dimer is found to decrease with increasing salt concentrations indicating that salt bridges play important roles in dimerization of the protein. Furthermore, the fluorescence measurement showed that Co(2+) ions play an important role in the local tertiary structure of the protein than Mn(2+). This is consistent with the pH-dependent studies where the Co(2+)-enzyme showed a single ionization compared to the double in the Mn(2+)-enzyme. Thus, this study presents the detailed biochemical and spectroscopic investigations into the differences in the biochemical properties and activity between H. pylori and other arginases. 相似文献
105.
Patterns in potassium dynamics in forest ecosystems 总被引:5,自引:0,他引:5
The biotic cycling of potassium (K) in forest systems has been relatively understudied in comparison with nitrogen (N) and phosphorus (P) despite its critical roles in maintaining the nutrition of primary production in forests. We investigated the ecological significance of K in forests from a literature review and data synthesis. We focused on (1) describing patterns of the effects of K availability on aboveground growth and change in foliar tissue of tree species from a variety of forests; and (2) documenting previously unreported relationships between hydrologic losses of K and N in forested watersheds from the Americas. In a review of studies examining tree growth under K manipulations/fertilizations, a high percentage (69% of studies) showed a positive response to increases in K availability in forest soils. In addition, 76% of the tree studies reviewed showed a positive and significant increase in K concentrations in plant tissue after soil K manipulation/fertilization. A meta-analysis on a subset of the reviewed studies was found to provide further evidence that potassium effects tree growth and increased tissue [K] with an effect size of 0.709 for growth and an overall effect size of 0.56. In our review of watershed studies, we observed that concentrations of K typically decreased during growing seasons in streams draining forested areas in the Temperate Zones and were responsive to vegetation disturbance in both temperate and tropical regions. We found a strong relationship (r2 = 0.42-0.99) between concentrations of K and N (another critical plant nutrient) in stream water, suggesting that similar mechanisms of biotic retention may control the flow of these nutrients. Furthermore, K dynamics appear to be unique among the base cations, e.g. calcium, magnesium, and sodium, because the others do not show similar seasonal patterns to K. We suggest that K may be important to the productivity and sustenance of many forests, and its dynamics and ecological significance warrant further study. We suggest that knowledge about the dynamics of this understudied element is imperative for our understanding patterns and processes in forest ecosystems. 相似文献
106.
Sujay Subbayya Ithychanda Mitali Das Yan-Qing Ma Keyang Ding Xiaoxia Wang Sudhiranjan Gupta Chuanyue Wu Edward F. Plow Jun Qin 《The Journal of biological chemistry》2009,284(7):4713-4722
The linkage of heterodimeric (α/β) integrin receptors with their
extracellular matrix ligands and intracellular actin cytoskeleton is a
fundamental step for controlling cell adhesion and migration. Binding of the
actin-linking protein, talin, to integrin β cytoplasmic tails (CTs)
induces high affinity ligand binding (integrin activation), whereas binding of
another actin-linking protein, filamin, to the integrin β CTs negatively
regulates this process by blocking the talin-integrin interaction. Here we
show structurally that migfilin, a novel cytoskeletal adaptor highly enriched
in the integrin adhesion sites, strongly interacts with the same region in
filamin where integrin β CTs bind. We further demonstrate that the
migfilin interaction dissociates filamin from integrin and promotes the
talin/integrin binding and integrin activation. Migfilin thus acts as a
molecular switch to disconnect filamin from integrin for regulating integrin
activation and dynamics of extracellular matrix-actin linkage.Cells reside in a protein network, the extracellular matrix
(ECM).4 Cell-ECM
contact is crucial for many physiological and pathophysiological processes and
is primarily mediated by heterodimeric (α/β) transmembrane
receptors, the integrins (1).
Integrins engage a variety of ECM proteins via their extracellular domains
while connecting to the actin cytoskeleton via their small cytoplasmic tails
(CTs). The ability of integrins to bind to their ligands is uniquely
controlled by the integrin CTs via a process called “inside-out
signaling,” i.e. upon cellular stimulation, an integrin,
typically expressed in a latent state, can receive intracellular signal(s) at
its CT, which transmits through the transmembrane domain to the extracellular
domain thereby converting the receptor from a low to a high affinity state
(integrin activation). How such long range information transfer is initiated
and regulated has been the central topic of integrin/cell adhesion research
over the decades (for reviews see Refs.
2-5).
Structural/biochemical studies have indicated that the inside-out signaling
involves the unclasping of the integrin α/β CT complex
(6-9),
followed by extensive rearrangement of transmembrane domain and extracellular
domain
(10-13).
Talin, a large actin-linking protein, was found to play a key role in the
unclasping process by binding to the integrin β CTs
(7-8,
14). Talin activity appears to
be controlled by multiple factors or pathways
(15-20).Relevant to this study is the role of filamin, another major actin
cross-linking protein
(21-22),
in integrin activation. Filamin was found to share an overlapping binding site
on integrin β CTs with talin and thus suppress the talin-integrin
interaction (16). Gene
silencing of filamin in various cell lines to remove the filamin-integrin
connection enhances integrin activation
(16,
23), whereas increased
filamin-integrin interaction inhibits cell migration
(24), a process critically
dependent on integrin activation. Together these observations support the
notion that filamin binding to integrin serves as a cellular brake to control
the dynamics of the integrin activation by inhibiting talin function and
ECM-cytoskeleton communication. The mechanism as to how the filamin brake is
turned off to promote integrin activation and cell migration is not
understood.Filamin is known to contain an N-terminal actin binding domain (ABD) and a
long rod-like domain of 24 immunoglobulin-like repeats, of which repeat 21
(IgFLN21) was shown to play a key role in binding to integrin β CTs and
blocking the talin-integrin β CT interaction
(16). Interestingly, IgFLN21
also recognizes another intracellular protein called migfilin, which has been
shown to be an important regulator of integrin-mediated cytoskeletal
rearrangements, cell shape change
(25), and cell migration
(26).In an effort to dissect the complex intermolecular interactions between
migfilin, filamin, and integrin, we have undertaken a detailed
structural/functional analysis. Using NMR spectroscopy, we have mapped the
precise IgFLN21 binding region in migfilin, which is located at the extreme N
terminus (residues 1-24) of migfilin (migfilin-N), and we solved solution
structure of the IgFLN21-migfilin-N complex. To our surprise, despite little
sequence homology, migfilin binds to the same region in IgFLN21 where integrin
β CT binds. Detailed NMR and biochemical analyses demonstrate that the
migfilin-filamin interaction is an order of magnitude higher than the
integrin-filamin interaction and that the migfilin binding to filamin can
competitively dissociate filamin from integrin and thus promote the
talin-integrin interaction. Using multiple functional approaches, we further
show that migfilin, but not its filamin binding defective mutant,
significantly enhances integrin activation. These data suggest a novel
regulatory pathway in which the binding of filamin to its downstream target
migfilin switches off the integrin-filamin connection, thereby promoting talin
binding to and activation of integrins. 相似文献
107.
Nazish Abdullah Bharani Srinivasan Nir Modiano Apurba Kumar Sau 《Journal of molecular biology》2009,386(3):690-298
Unlike other GTPases, interferon-gamma-induced human guanylate binding protein-1 has the ability to hydrolyze GTP to both GDP and GMP, with GMP being the major product of the reaction. This protein has two domains, an N-terminal globular domain and a C-terminal helical domain. These two domains are connected by a short intermediate region consisting of a two-stranded β-sheet and a helix. As human guanylate binding protein-1 has been shown to undergo stimulated GTPase activity without external GTPase-activating protein, we sought to understand the roles of each of the two individual domains, the intermediate region, a conserved motif (103DXEKGD108), and the mechanism of the stimulation of GTPase activity. The steady-state assays using radiolabeled [α-32P]GTP on the wild-type protein suggest that the stimulation of activity primarily occurs during the cleavage of the second phosphate of GTP rather than the first, through allosteric interaction. Using several truncated and mutant proteins, we demonstrate for the first time that both the α-helix of the intermediate region and the 103DXEKGD108 motif play critical roles for the hydrolysis to GMP, but they appear to act in different ways: α-helix acts through structural stabilization by allosteric interaction and, thus, acts as an internal GTPase-activating protein, whereas the motif might act by providing necessary catalytic residues. Our data also show that the N-terminal globular domain is able to perform only the first catalysis (GTP to GDP, an activity associated with basal level), but the helical domain in the full-length protein stimulates the hydrolysis of GTP to GMP with higher GMP formation by preventing the dissociation of GDP-bound enzyme dimer. 相似文献
108.
FKBP22, a protein expressed by Escherichia coli, possesses PPIase (peptidyl-prolyl cis-trans isomerase) activity, binds FK506 (an immunosuppressive drug), and shares homology with Legionella Mip (a virulence factor) and its related proteins. To understand the domain structure and the folding-unfolding mechanism of Mip-like proteins, we investigated a recombinant E. coli FKBP22 (His-FKBP22) as a model protein. Limited proteolysis indicated that His-FKBP22 harbors an N-terminal domain (NTD), a C-terminal domain (CTD), and a long flexible region linking the two domains. His-FKBP22, NTD(+) (NTD with the entire flexible region), and CTD(+) (CTD with a truncated flexible region) were unfolded by a two-state mechanism in the presence of urea. Urea induced the swelling of dimeric His-FKBP22 molecules at the pretransition state but dissociated it at the early transition state. In contrast, guanidine hydrochloride (GdnCl)-induced equilibrium unfolding of His-FKBP22 or NTD(+) and CTD(+) seemed to follow three-step and two-step mechanisms, respectively. Interestingly, the intermediate formed during the unfolding of His-FKBP22 with GdnCl was not a molten globule but was thought to be composed of the partially unfolded dimeric as well as various multimeric His-FKBP22 molecules. Dimeric His-FKBP22 did not dissociate gradually with increasing concentrations of GdnCl. Very low GdnCl concentrations also had little effect on the molecular dimensions of His-FKBP22. Unfolding with either denaturant was found to be reversible, as refolding of the unfolded His-FKBP22 completely, or nearly completely, restored the structure and function of the protein. Additionally, denaturation of His-FKBP22 appeared to begin at the CTD(+). 相似文献
109.
S Chattopadhyay S Paul DI Kisiela EV Linardopoulou EV Sokurenko 《Journal of bacteriology》2012,194(18):5002-5011
One of the strongest signals of adaptive molecular evolution of proteins is the occurrence of convergent hot spot mutations: repeated changes in the same amino acid positions. We performed a comparative genome-wide analysis of mutation-driven evolution of core (omnipresent) genes in 17 strains of Salmonella enterica subspecies I and 22 strains of Escherichia coli. More than 20% of core genes in both Salmonella and E. coli accumulated hot spot mutations, with a predominance of identical changes having recent evolutionary origin. There is a significant overlap in the functional categories of the adaptively evolving genes in both species, although mostly via separate molecular mechanisms. As a strong evidence of the link between adaptive mutations and virulence in Salmonella, two human-restricted serovars, Typhi and Paratyphi A, shared the highest number of genes with serovar-specific hot spot mutations. Many of the core genes affected by Typhi/Paratyphi A-specific mutations have known virulence functions. For each species, a list of nonrecombinant core genes (and the hot spot mutations therein) under positive selection is provided. 相似文献
110.
Kelly A. Collins Timothy J. Lawrence Emilie K. Stander Robert J. Jontos Sujay S. Kaushal Tamara A. Newcomer Nancy B. Grimm Marci L. Cole Ekberg 《Ecological Engineering》2010,36(11):1507-1519
Although nitrogen (N) is prevalent in urban stormwater, regulation of this pollutant has occurred only more recently. This paper reviews the concerns over N in urban stormwater, mechanisms and design enhancements for N uptake and denitrification through various stormwater control measures (SCMs), and presents opportunities to integrate this current knowledge into the regulatory framework. A survey of personnel directly involved in various aspects of US state and territory NPDES programs revealed that the top three pollutants of concern were total suspended solids (TSS), pathogens and bacteria, and total phosphorus (TP). Surprisingly, nitrate (NO3?) was of little concern among the survey respondents, with 3.9% giving it the highest level of concern, 2.0% ranking it second, and 6.0% ranking it third. When asked which strategies were currently used in their geographic area for stormwater management, the most common results were wet ponds and dry ponds. At the same time, wet ponds and dry ponds were recognized as less effective practices to manage stormwater.A review of current literature reveals that several alternative SCMs, such as bioretention, filters, and wetlands, show greater promise in their ability to remove N from stormwater than more conventional practices such as dry ponds and wet ponds. Enhanced N removal via denitrification and plant uptake is often observed under the combination of aerobic followed by sustained anoxic conditions, the presence of a carbon source (organic material), and the presence of mature, dense vegetation.Given the lack of concern or awareness of local officials related to N loading from urban stormwater, and variation in the efficacy of various SCMs, it is not surprising that regulators remain focused on conventional dry pond and wet pond control measures. More needs to be done to quantify the impact of urban sources of N on water quality and aquatic ecosystems. In addition, greater focus needs to be placed on the development of design criteria for SCMs, such as bioretention, filters, and constructed wetlands, which show more promise for N removal. 相似文献