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排序方式: 共有112条查询结果,搜索用时 15 毫秒
1.
Sewell BT Best RB Chen S Roseman AM Farr GW Horwich AL Saibil HR 《Nature structural & molecular biology》2004,11(11):1128-1133
The chaperonin GroEL assists protein folding through ATP-dependent, cooperative movements that alternately create folding chambers in its two rings. The substitution E461K at the interface between these two rings causes temperature-sensitive, defective protein folding in Escherichia coli. To understand the molecular defect, we have examined the mutant chaperonin by cryo-EM. The normal out-of-register alignment of contacts between subunits of opposing wild-type rings is changed in E461K to an in-register one. This is associated with loss of cooperativity in ATP binding and hydrolysis. Consistent with the loss of negative cooperativity between rings, the cochaperonin GroES binds simultaneously to both E461K rings. These GroES-bound structures were unstable at higher temperature, dissociating into complexes of single E461K rings associated with GroES. Lacking the allosteric signal from the opposite ring, these complexes cannot release their GroES and become trapped, dead-end states. 相似文献
2.
A recent meeting brought together electron microscopists, crystallographers and modellers to consider the problems facing structural biologists who wish to understand large, subcellular machines, and how the methods should be extended to achieve this goal. 相似文献
3.
Conformational changes studied by cryo-electron microscopy 总被引:1,自引:0,他引:1
Saibil HR 《Nature structural biology》2000,7(9):711-714
Biological processes involving movement, such as muscle contraction or the opening of an ion channel through a membrane, are mediated through conformational changes. These changes often occur in large and flexible macromolecular complexes. Cryo-electron microscopy provides a means of capturing different conformational states of such assemblies. Even if the resulting density maps are at low resolution, they can be combined with atomic structures of subcomplexes or isolated components determined by X-ray crystallography or NMR. This review presents a brief summary of the principles and recent advances in macromolecular structure determination by cryo-electron microscopy. 相似文献
4.
TIP48 and TIP49 are two related and highly conserved eukaryotic AAA(+) proteins with an essential biological function and a critical role in major pathways that are closely linked to cancer. They are found together as components of several highly conserved chromatin-modifying complexes. Both proteins show sequence homology to bacterial RuvB but the nature and mechanism of their biochemical role remain unknown. Recombinant human TIP48 and TIP49 were assembled into a stable high molecular mass equimolar complex and tested for activity in vitro. TIP48/TIP49 complex formation resulted in synergistic increase in ATPase activity but ATP hydrolysis was not stimulated in the presence of single-stranded, double-stranded or four-way junction DNA and no DNA helicase or branch migration activity could be detected. Complexes with catalytic defects in either TIP48 or TIP49 had no ATPase activity showing that both proteins within the TIP48/TIP49 complex are required for ATP hydrolysis. The structure of the TIP48/TIP49 complex was examined by negative stain electron microscopy. Three-dimensional reconstruction at 20 A resolution revealed that the TIP48/TIP49 complex consisted of two stacked hexameric rings with C6 symmetry. The top and bottom rings showed substantial structural differences. Interestingly, TIP48 formed oligomers in the presence of adenine nucleotides, whilst TIP49 did not. The results point to biochemical differences between TIP48 and TIP49, which may explain the structural differences between the two hexameric rings and could be significant for specialised functions that the proteins perform individually. 相似文献
5.
Topologies of a substrate protein bound to the chaperonin GroEL 总被引:3,自引:0,他引:3
The chaperonin GroEL assists polypeptide folding through sequential steps of binding nonnative protein in the central cavity of an open ring, via hydrophobic surfaces of its apical domains, followed by encapsulation in a hydrophilic cavity. To examine the binding state, we have classified a large data set of GroEL binary complexes with nonnative malate dehydrogenase (MDH), imaged by cryo-electron microscopy, to sort them into homogeneous subsets. The resulting electron density maps show MDH associated in several characteristic binding topologies either deep inside the cavity or at its inlet, contacting three to four consecutive GroEL apical domains. Consistent with visualization of bound polypeptide distributed over many parts of the central cavity, disulfide crosslinking could be carried out between a cysteine in a bound substrate protein and cysteines substituted anywhere inside GroEL. Finally, substrate binding induced adjustments in GroEL itself, observed mainly as clustering together of apical domains around sites of substrate binding. 相似文献
6.
Macromolecules may occupy conformations with structural differences that cannot be resolved biochemically. The separation of mixed molecular populations is a pressing problem in single-particle analysis. Until recently, the task of distinguishing small structural variations was intractable, but developments in cryo-electron microscopy hardware and software now make it possible to address this problem. We have developed a general strategy for recognizing and separating structures of variable size from cryo-electron micrographs of single particles. The method uses a combination of statistical analysis and projection matching to multiple models. Identification of size variations by multivariate statistical analysis was used to do an initial separation of the data and generate starting models by angular reconstitution. Refinement was performed using alternate projection matching to models and angular reconstitution of the separated subsets. The approach has been successful at intermediate resolution, taking it within range of resolving secondary structure elements of proteins. Analysis of simulated and real data sets is used to illustrate the problems encountered and possible solutions. The strategy developed was used to resolve the structures of two forms of a small heat shock protein (Hsp26) that vary slightly in diameter and subunit packing. 相似文献
7.
Genetic and environmental heterogeneity of residual variance of weight traits in Nellore beef cattle
Background
Many studies have provided evidence of the existence of genetic heterogeneity of environmental variance, suggesting that it could be exploited to improve robustness and uniformity of livestock by selection. However, little is known about the perspectives of such a selection strategy in beef cattle.Methods
A two-step approach was applied to study the genetic heterogeneity of residual variance of weight gain from birth to weaning and long-yearling weight in a Nellore beef cattle population. First, an animal model was fitted to the data and second, the influence of additive and environmental effects on the residual variance of these traits was investigated with different models, in which the log squared estimated residuals for each phenotypic record were analyzed using the restricted maximum likelihood method. Monte Carlo simulation was performed to assess the reliability of variance component estimates from the second step and the accuracy of estimated breeding values for residual variation.Results
The results suggest that both genetic and environmental factors have an effect on the residual variance of weight gain from birth to weaning and long-yearling in Nellore beef cattle and that uniformity of these traits could be improved by selecting for lower residual variance, when considering a large amount of information to predict genetic merit for this criterion. Simulations suggested that using the two-step approach would lead to biased estimates of variance components, such that more adequate methods are needed to study the genetic heterogeneity of residual variance in beef cattle. 相似文献8.
9.
Ira R. Kim Kiichi Murakami Nien-Jung Chen Samuel D. Saibil Elzbieta Matysiak-Zablocki Alisha R. Elford Madeleine Bonnard Samuel Benchimol Andrea Jurisicova Wen-Chen Yeh Pamela S. Ohashi 《Apoptosis : an international journal on programmed cell death》2009,14(9):1039-1049
The p53-induced protein with a death domain, PIDD, was identified as a p53 target gene whose main role is to execute apoptosis
in a p53-dependent manner. To investigate the physiological role of PIDD in apoptosis, we generated PIDD-deficient mice. Here,
we report that, although PIDD expression is inducible upon DNA damage, PIDD-deficient mice undergo apoptosis normally not
only in response to DNA damage, but also in response to various p53-independent stress signals and to death receptor (DR)
engagement. This indicates that PIDD is not required for DNA damage-, stress-, and DR-induced apoptosis. Also, in the absence
of PIDD, both caspase-2 processing and activation occur in response to DNA damage. Our findings demonstrate that PIDD does
not play an essential role for all p53-mediated or p53-independent apoptotic pathways.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
10.
Multiple distinct assemblies reveal conformational flexibility in the small heat shock protein Hsp26
White HE Orlova EV Chen S Wang L Ignatiou A Gowen B Stromer T Franzmann TM Haslbeck M Buchner J Saibil HR 《Structure (London, England : 1993)》2006,14(7):1197-1204
Small heat shock proteins are a superfamily of molecular chaperones that suppress protein aggregation and provide protection from cell stress. A key issue for understanding their action is to define the interactions of subunit domains in these oligomeric assemblies. Cryo-electron microscopy of yeast Hsp26 reveals two distinct forms, each comprising 24 subunits arranged in a porous shell with tetrahedral symmetry. The subunits form elongated, asymmetric dimers that assemble via trimeric contacts. Modifications of both termini cause rearrangements that yield a further four assemblies. Each subunit contains an N-terminal region, a globular middle domain, the alpha-crystallin domain, and a C-terminal tail. Twelve of the C termini form 3-fold assembly contacts which are inserted into the interior of the shell, while the other 12 C termini form contacts on the surface. Hinge points between the domains allow a variety of assembly contacts, providing the flexibility required for formation of supercomplexes with non-native proteins. 相似文献