Temperature-dependent study reveals that dynamics of hydrophobic residues plays an important functional role in the mitochondrial Tim9–Tim10 complex
Ekaterina Ivanova
Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
The authors contribute equally to the work.
Search for more papers by this authorJiayun Pang
Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom
School of Chemical Engineering and Analytical Science, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom
The authors contribute equally to the work.
Search for more papers by this authorThomas A. Jowitt
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
Search for more papers by this authorGuanhua Yan
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
Search for more papers by this authorJim Warwicker
Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
Search for more papers by this authorMichael J. Sutcliffe
Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom
School of Chemical Engineering and Analytical Science, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom
Search for more papers by this authorCorresponding Author
Hui Lu
Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom===Search for more papers by this authorEkaterina Ivanova
Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
The authors contribute equally to the work.
Search for more papers by this authorJiayun Pang
Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom
School of Chemical Engineering and Analytical Science, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom
The authors contribute equally to the work.
Search for more papers by this authorThomas A. Jowitt
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
Search for more papers by this authorGuanhua Yan
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
Search for more papers by this authorJim Warwicker
Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
Search for more papers by this authorMichael J. Sutcliffe
Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom
School of Chemical Engineering and Analytical Science, University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom
Search for more papers by this authorCorresponding Author
Hui Lu
Manchester Interdisciplinary Biocentre, University of Manchester, Manchester M1 7DN, United Kingdom
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, United Kingdom
Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom===Search for more papers by this authorAbstract
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.
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