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31.
32.
Galkin VE Orlova A Lukoyanova N Wriggers W Egelman EH 《The Journal of cell biology》2001,152(1):75-86
Proteins in the actin depolymerizing factor (ADF)/cofilin family are essential for rapid F-actin turnover, and most depolymerize actin in a pH-dependent manner. Complexes of human and plant ADF with F-actin at different pH were examined using electron microscopy and a novel method of image analysis for helical filaments. Although ADF changes the mean twist of actin, we show that it does this by stabilizing a preexisting F-actin angular conformation. In addition, ADF induces a large ( approximately 12 degrees ) tilt of actin subunits at high pH where filaments are readily disrupted. A second ADF molecule binds to a site on the opposite side of F-actin from that of the previously described ADF binding site, and this second site is only largely occupied at high pH. All of these states display a high degree of cooperativity that appears to be an integral part of F-actin. 相似文献
33.
Alicia Alonso Colin J. Restall Margaret Turner Juan C. Gomez-Fernandez Felix M. Goñi Dennis Chapman 《生物化学与生物物理学报:生物膜》1982,689(2):283-289
Bacteriorhodopsin has been reconstituted at various molar concentrations into liposomes of dimyristoyl- and also of dipalmitoylphosphatidylcholine. Differential scanning calorimetry indicates that as the protein concentration within the lipid bilayer increases, the cooperativity of the lipid phase transition is reduced, i.e. the transition is broadened, while the midpoint transition temperature remains virtually unchanged. Freeze-fracture electron microscopy of our preparation shows, in agreement with previous data from other laboratories, that extensive protein aggregation occurs when the liposome is cooled below the Tc transition temperature of the lipid. Laser flash photolysis measurements of protein rotation of the bacteriorhodopsin show, especially in the case of protein-rich recombinants, that protein aggregates exist even above Tc. The perturbation caused by the presence of bacteriorhodopsin in the lipid bilayer is similar to that produced by other intrinsic proteins. The difficulty of correlating the observed calorimetric enthalpy data with a simple concept of a ‘boundary lipid layer’ based upon consideration of a single isolated protein is discussed in view of the occurrence of protein aggregates both above and below Tc. It is concluded that the reduction of enthalpy is related to the number of lipids which solvate the protein aggregates within the protein-lipid patches and are thereby removed from the cooperative melting and enthalpy of the remaining regions of pure lipid. 相似文献
34.
35.
Clark LA 《Protein science : a publication of the Protein Society》2005,14(3):653-662
Two-chain aggregation simulations using minimalist models of proteins G, L, and mutants were used to investigate the fundamentals of protein aggregation. Mutations were selected to break up repeats of hydrophobic beads in the sequence while maintaining native topology and folding ability. Data are collected under conditions in which all chain types have similar folded populations and after equilibrating the separated chains to minimize competition between folding and aggregation. Folding cooperativity stands out as the best single-chain determinant under these conditions and for these simple models. It can be experimentally measured by the width of the unfolding transition during thermal denaturation and loosely related to population of intermediate-like states during folding. Additional measures of cooperativity and other properties such as radius of gyration fluctuations and patterning of hydrophobic residues are also examined. Initial contact system states with transition-state characteristics can be identified and are more expanded than average initial contact states. Two-chain minimalist model aggregates are considerably less structured than their native states and have minimal domain-swapping features. 相似文献
36.
There are currently two contradictory models for the kinetics of the ATP-induced GroEL allosteric transition occurring around 20 microM ATP. One model, proposed by Horovitz et al. demonstrates the existence of two parallel pathways for the allosteric transition and an abrupt ATP-dependent switch from one pathway to the other. The other model, which was proposed by the present authors, shows no need to assume the parallel pathways, and a combination of the transition-state theory and the Monod-Wyman-Changeux model of allostery can explain the kinetics as well as the equilibrium of the transition. The discrepancy appears to be due to whether we regard the transition as reversible or irreversible. Thus, here we have investigated the reversibility of the allosteric transition between 0 microM and 70 microM ATP by the use of a stopped-flow double-jump technique, which has allowed us to monitor the kinetics of the reverse reaction from the relaxed state at a high ATP concentration to the tense state at a low ATP concentration. The tryptophan fluorescence of a tryptophan-inserted variant of GroEL was used to follow the kinetics. As a result, the allosteric transition was shown to be a reversible process, supporting the validity of our model. We also show that the structural environment around the ATP-binding site of GroEL in the transition state is very similar to that in the relaxed state (Phi=0.9) by using a Phi value analysis in the kinetic Monod-Wyman-Changeux model, which is analogous to the mutational Phi value analysis in protein folding. 相似文献
37.
As molecules approach one another in aqueous solution, desolvation free energy barriers to association are encountered. Experiments suggest these (de)solvation effects contribute to the free energy barriers separating the folded and unfolded states of protein molecules. To explore their influence on the energy landscapes of protein folding reactions, we have incorporated desolvation barriers into a semi-realistic, off-lattice protein model that uses a simplified physico-chemical force-field determined solely by the sequence of amino acids. Monte Carlo sampling techniques were used to study the effects on the thermodynamics and kinetics of folding of a number of systems, diverse in structure and sequence. In each case, desolvation barriers increase the stability of the native conformation and the cooperativity of the major folding/unfolding transition. The folding times of these systems are reduced significantly upon inclusion of desolvation barriers, demonstrating that the particulate nature of the solvent engenders a more defined route to the native fold. 相似文献
38.
Oligomeric potential of the M2 muscarinic cholinergic receptor 总被引:1,自引:0,他引:1
G protein-coupled receptors are known to exist as oligomers. Although such aggregates often are referred to as dimers, there is little direct evidence regarding their oligomeric size. In the present investigation, c-Myc-, FLAG-, and influenza hemagglutinin (HA)-tagged forms of the M2 muscarinic receptor have been coexpressed in Sf9 cells to probe for aggregates larger than a dimer. Immunochromatography, immunoprecipitation, and immunoblotting were carried out with various combinations of antibodies directed against the different epitopes to demonstrate that all three tagged forms of the receptor can be immunopurified within a single complex. Extracts of the M2 muscarinic receptor from Sf9 cells therefore contain aggregates that are at least trimeric, and the levels detected point to the existence of larger complexes. The data also suggest that the oligomers coexist with a sizeable population of monomers. 相似文献
39.
Monika Świniarska Andrzej Leś Wojciech Rode Joanna Cieśla César Millán‐Pacheco Iván Ortega Blake Nina Pastor 《Biopolymers》2010,93(6):549-559
Thymidylate synthase (TS) is a homodimeric enzyme with two equivalent active sites composed of residues from both subunits. Despite the structural symmetry of the enzyme, certain experimental results are consistent with half‐the‐sites activity, suggesting negative cooperativity between the active sites. To gain insight into the mechanism behind this phenomenon, we explore segmental motions of rat TS in the absence of ligands, with normal mode analysis as a tool. Using solvent accessible surface area of the active site pocket as a monitor of the degree of opening of the active sites, we classified the first 25 nontrivial normal modes, obtained from the web server of the program ElNémo, according to the behavior of the active sites. We found seven modes that open and close both sites symmetrically and nine that do so in an anticorrelated fashion. We characterized the motions of these modes by visual inspection and through measurement of distances between selected atoms lining the active site pockets. The segments that regulate access to the active site correspond to the loop containing R44, helix K, and a long loop containing residues 103–125, in agreement with a large body of crystallographic studies. These elements can be activated together or in isolation. There are more asymmetric modes than symmetric ones in the set we analyzed, probably accounting for the half‐the‐sites behavior of the enzyme. Three of the asymmetric modes result in changes at the dimer interface and indicate the endpoints of possible communication pathways between the active sites. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 549–559, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com 相似文献
40.
Carey J Benoff B Harish B Yuan L Lawson CL 《Protein science : a publication of the Protein Society》2012,21(1):63-74
Extensive environment-dependent rearrangement of the helix-turn-helix DNA recognition region and adjacent L-tryptophan binding pocket is reported in the crystal structure of dimeric E. coli trp aporepressor with point mutation Leu75Phe. In one of two subunits, the eight residues immediately C-terminal to the mutation are shifted forward in helical register by three positions, and the five following residues form an extrahelical loop accommodating the register shift. In contrast, the second subunit has wildtype-like conformation, as do both subunits in an isomorphous wildtype control structure. Treated together as an ensemble pair, the distorted and wildtype-like conformations of the mutant apoprotein agree more fully than either conformation alone with previously reported NOE measurements, and account more completely for its diverse biochemical and biophysical properties. The register-shifted segment Ile79-Ala80-Thr81-Ile82-Thr83 is helical in both conformations despite low helical propensity, suggesting an important structural role for the steric constraints imposed by β-branched residues in helical conformation. 相似文献