期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：9
页码：4099-4104
DOI：10.1073/pnas.0911904107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Inspired by the seminal work of Anfinsen, investigations of the folding of small water-soluble proteins have culminated in detailed insights into how these molecules attain and stabilize their native folds. In contrast, despite their overwhelming importance in biology, progress in understanding the folding and stability of membrane proteins remains relatively limited. Here we use mutational analysis to describe the transition state involved in the reversible folding of the {beta}-barrel membrane protein PhoPQ-activated gene P (PagP) from a highly disordered state in 10 M urea to a native protein embedded in a lipid bilayer. Analysis of the equilibrium stability and unfolding kinetics of 19 variants that span all eight {beta}-strands of this 163-residue protein revealed that the transition-state structure is a highly polarized, partly formed {beta}-barrel. The results provide unique and detailed insights into the transition-state structure for {beta}-barrel membrane protein folding into a lipid bilayer and are consistent with a model for outer membrane protein folding via a tilted insertion mechanism.
关键词：beta barrel ; membrane protein ; PagP ; phi-value analysis ; protein folding
