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通过将φ值与残基间接触进行关联来解析蛋白质折叠途径的结构分辨率。

Structural resolution of the folding pathway of a protein by correlation of phi-values with inter-residue contacts.

作者信息

Nölting B

机构信息

Prussian Private Institute of Technology at Berlin, Görschstr 40, D-13187 Berlin, Germany.

出版信息

J Theor Biol. 1998 Oct 7;194(3):419-28. doi: 10.1006/jtbi.1998.0783.

DOI:10.1006/jtbi.1998.0783
PMID:9778447
Abstract

Folding of barstar, the 10 kDalton inhibitor of the ribonuclease barnase, has been suggested to follow a nucleation-condensation model [Nölting, B., Golbik, R., Neira, J. L., Soler-Gonzalez, A. S., Schreiber, G. & Fersht, A. R. (1997). Proc. Nat. Acad. Sci. U.S.A. 94, 826-830], where structure growth starts in a particular region of the molecule, the folding nucleus. Here the structure of the diffuse nucleus and its growth in three stages, 500 micros, 1 ms and 100 ms after initiation of the folding reaction, is mapped out by using phi-values which are correlate with inter-residue contact plots. Barstar folding is initiated by a significant consolidation of interactions in and around the strand1-loop1-helix1 motif in the microsecond time scale, followed by the consolidation of helix4, which is located close to the C-terminus and does not have significant residual structure in the cold-denatured state. The non-uniform structure consolidation is most pronounced in the early stages of folding. The late folding events of barstar are characterized by a propagation of structure consolidation from the N-and C-termini towards residues located in the center of the sequence.

摘要

核糖核酸酶barnase的10千道尔顿抑制剂barstar的折叠,被认为遵循成核-凝聚模型【诺尔廷,B.,戈尔比克,R.,内拉,J. L.,索勒-冈萨雷斯,A. S.,施赖伯,G. & 弗什特,A. R.(1997年)。《美国国家科学院院刊》94,826 - 830】,其中结构生长始于分子的特定区域,即折叠核。在此,通过使用与残基间接触图相关的φ值,描绘了折叠反应开始后500微秒、1毫秒和100毫秒这三个阶段中扩散核的结构及其生长情况。Barstar折叠在微秒时间尺度上由strand1-loop1-helix1基序及其周围相互作用的显著巩固引发,随后是靠近C端且在冷变性状态下没有显著残余结构的螺旋4的巩固。结构巩固的不均匀性在折叠早期最为明显。Barstar的后期折叠事件的特征是结构巩固从N端和C端向序列中心的残基传播。

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