Quantifying the structural requirements of the folding transition state of protein A and other systems

JOURNAL OF MOLECULAR BIOLOGY

卷:381

Review

Baxa, Michael C.^2,3  Freed, Karl F.^4,5  Sosnick, Tobin R.^1,3 

[1] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA

[2] Univ Chicago, Dept Phys, Chicago, IL 60637 USA

[3] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA

[4] Univ Chicago, James Franck Inst, Chicago, IL 60637 USA

[5] Univ Chicago, Dept Chem, Chicago, IL 60637 USA

关键词: protein folding;    BdpA;    phi analysis;    contact order;    psi analysis;   

DOI  :  10.1016/j.jmb.2008.06.067

来源: Elsevier

【 摘 要 】

The B-domain of protein A is a small. three-helix bundle that has been the subject of considerable experimental and theoretical investigation. Nevertheless, a unified view of the structure of the transition-state ensemble (TSE) is still lacking. To characterize the TSE of this surprisingly challenging protein, we apply a combination of psi analysis (which probes the role of specific side-chain to side-chain contacts) and kinetic H/D amide isotope effects (which measures hydrogen-bond content), building upon previous studies using mutational phi analysis (which probes the energetic influence of side-chain substitutions). The second helix is folded in the TSE, while helix formation appears just at the carboxy and amino termini of the first and third helices, respectively. The experimental data suggest a homogenous yet plastic TS with a native-like topology. This study generalizes our earlier conclusion, based on two larger alpha/beta proteins, that the TSEs of most small proteins achieve similar to 70% of their native state's relative contact order. This high percentage limits the degree of possible TS heterogeneity and requires a reevaluation of the structural content of the TSE of other proteins, especially when they are characterized as small or polarized. (c) 2008 Elsevier Ltd. All rights reserved.

【 授权许可】

Free