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Temperature‐dependent study reveals that dynamics of hydrophobic residues plays an important functional role in the mitochondrial Tim9–Tim10 complex
Author(s) -
Ivanova Ekaterina,
Pang Jiayun,
Jowitt Thomas A.,
Yan Guanhua,
Warwicker Jim,
Sutcliffe Michael J.,
Lu Hui
Publication year - 2012
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.23224
Subject(s) - intermembrane space , translocase , molecular dynamics , chemistry , biophysics , hydrophobic effect , protein–protein interaction , function (biology) , mitochondrial intermembrane space , inner mitochondrial membrane , chemical physics , membrane , bacterial outer membrane , computational chemistry , biology , biochemistry , microbiology and biotechnology , chromosomal translocation , escherichia coli , gene
Protein–protein interaction is a fundamental process in all major biological processes. The hexameric Tim9–Tim10 (translocase of inner membrane) complex of the mitochondrial intermembrane space plays an essential chaperone‐like role during import of mitochondrial membrane proteins. However, little is known about the functional mechanism of the complex because the interaction is weak and transient. This study investigates how electrostatic and hydrophobic interactions affect the conformation and function of the complex at physiological temperatures, using both experimental and computational methods. The results suggest that, first, different complex conformational states exist at equilibrium, and the major difference between these states is the degree of hydrophobic interactions. Second, the conformational change mimics the biological activity of the complex as measured by substrate binding at the same temperatures. Finally, molecular dynamics simulation and detailed energy decomposition analysis provided supporting evidence at the atomic level for the presence of an excited state of the complex, the formation of which is largely driven by the disruption of hydrophobic interactions. Taken together, this study indicates that the dynamics of the hydrophobic residues plays an important role in regulating the function of the Tim9–Tim10 complex. Proteins 2012. © 2011 Wiley Periodicals, Inc.