Understanding the heterogeneity intrinsic to protein folding

被引:4
作者
Bhatia, Sandhya [1 ]
Udgaonkar, Jayant B. [2 ]
机构
[1] UT Southwestern Med Ctr, Howard Hughes Med Inst, Dept Biophys, Dallas, TX 75390 USA
[2] Indian Inst Sci Educ & Res Pune, Dept Biol, Pune 411008, India
关键词
Protein folding; Conformational heterogeneity; Folding pathways; Intermediate ensemble; Time-resolved FRET; PULSED HYDROGEN-EXCHANGE; SINGLE-CHAIN MONELLIN; MULTIPLE PATHWAYS; KINETICS; NMR; INTERMEDIATE; DYNAMICS;
D O I
10.1016/j.sbi.2023.102738
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Relating the native fold of a protein to its amino acid sequence remains a fundamental problem in biology. While computer algorithms have demonstrated recently their prowess in predicting what structure a particular amino acid sequence will fold to, an understanding of how and whya specific protein fold is achieved remains elusive. A major challenge is to define the role of conformational heterogeneity during protein folding. Recent experimental studies, utilizing time-resolved FRET, hydrogen-exchange coupled to mass spectrometry, and single-molecule force spectroscopy, often in conjunction with simu-lation, have begun to reveal how conformational heterogeneity evolves during folding, and whether an intermediate ensemble of defined free energy consists of different sub-populations of molecules that may differ significantly in conformation, energy and entropy.
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页数:8
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