The Folding Transition State of Protein L Is Extensive with Nonnative Interactions (and Not Small and Polarized)

JOURNAL OF MOLECULAR BIOLOGY

卷:420

Article

Yoo, Tae Yeon²  Adhikari, Aashish^1,3  Xia, Zhen⁵  Huynh, Tien⁵  Freed, Karl F.^1,3,4  Zhou, Ruhong⁵  Sosnick, Tobin R.^4,6 

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

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

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

[4] Univ Chicago, Computat Inst, Chicago, IL 60637 USA

[5] IBM Corp, Thomas J Watson Res Ctr, Computat Biol Ctr, Yorktown Hts, NY 10598 USA

[6] Univ Chicago, Dept Biochem & Mol Biol, Inst Biophys Dynam, Chicago, IL 60637 USA

关键词: phi analysis;    psi analysis;    metal binding;    bi-histidine;    protein folding;   

DOI  :  10.1016/j.jmb.2012.04.013

来源: Elsevier

【 摘 要 】

Progress in understanding protein folding relies heavily upon an interplay between experiment and theory. In particular, readily interpretable experimental data that can be meaningfully compared to simulations are required. According to standard mutational phi analysis, the transition state for Protein L contains only a single hairpin. However, we demonstrate here using psi analysis with engineered metal ion binding sites that the transition state is extensive, containing the entire. four-stranded beta sheet. Under-reporting of the structural content of the transition state by phi analysis also occurs for acyl phosphatase [Pandit, A. D., Jha, A., Freed, K. F. & Sosnick, T. R., (2006). Small proteins fold through transition states with native-like topologies. J. Mol. Biol. 361, 755-770], ubiquitin [Sosnick, T. R., Dothager, R. S. & Krantz, B. A., (2004). Differences in the folding transition state of ubiquitin indicated phi and psi analyses. Proc. Natl Acad. Sci. USA 101, 17377-17382] and BdpA [Baxa, M., Freed, K. F. & Sosnick, T. R., (2008). Quantifying the structural requirements of the folding transition state of protein A and other systems. J. Mol. Biol. 381, 1362-1381]. The carboxyterminal hairpin in the transition state of Protein L is found to be nonnative, a significant result that agrees with our Protein Data Bank-based backbone sampling and all-atom simulations. The nonnative character partially explains the failure of accepted experimental and native-centric computational approaches to adequately describe the transition state. Hence, caution is required even when an apparent agreement exists between experiment and theory, thus highlighting the importance of having alternative methods for characterizing transition states. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

Free