HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 31, 32904-32912, July 30, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/31/32904    most recent M404884200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Toogood, H. S. Articles by Leys, D. Search for Related Content PubMed PubMed Citation Articles by Toogood, H. S. Articles by Leys, D. Social Bookmarking                      What's this?

Extensive Domain Motion and Electron Transfer in the Human Electron Transferring Flavoprotein·Medium Chain Acyl-CoA Dehydrogenase Complex^*

Helen S. Toogood, Adam van Thiel, Jaswir Basran, Mike J. Sutcliffe, Nigel S. Scrutton, and David Leys

From the Department of Biochemistry, University of Leicester, Leicester LE1 7RH, United Kingdom

The crystal structure of the human electron transferring flavoprotein (ETF)·medium chain acyl-CoA dehydrogenase (MCAD) complex reveals a dual mode of protein-protein interaction, imparting both specificity and promiscuity in the interaction of ETF with a range of structurally distinct primary dehydrogenases. ETF partitions the functions of partner binding and electron transfer between (i) the recognition loop, which acts as a static anchor at the ETF·MCAD interface, and (ii) the highly mobile redox active FAD domain. Together, these enable the FAD domain of ETF to sample a range of conformations, some compatible with fast interprotein electron transfer. Disorders in amino acid or fatty acid catabolism can be attributed to mutations at the protein-protein interface. Crucially, complex formation triggers mobility of the FAD domain, an induced disorder that contrasts with general models of protein-protein interaction by induced fit mechanisms. The subsequent interfacial motion in the MCAD·ETF complex is the basis for the interaction of ETF with structurally diverse protein partners. Solution studies using ETF and MCAD with mutations at the protein-protein interface support this dynamic model and indicate ionic interactions between MCAD Glu²¹² and ETF Arg²⁴⁹ are likely to transiently stabilize productive conformations of the FAD domain leading to enhanced electron transfer rates between both partners.

Received for publication, May 3, 2004 , and in revised form, May 17, 2004.

The atomic coordinates and structure factors (code 1T9G) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported by the United Kingdom Biotechnology and Biological Sciences Research Council. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Lister Institute Research Professor.

Royal Society University Research Fellow. To whom correspondence should be addressed: Dept. of Biochemistry, University Road, University of Leicester, Leicester LE1 7RH, UK. Tel.: 44-116-252-3484; Fax: 44-116-252-3369; E-mail: dl37{at}le.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Mackenzie, L. Pedersen, S. Arent, and A. Henriksen Controlling Electron Transfer in Acyl-CoA Oxidases and Dehydrogenases: A STRUCTURAL VIEW J. Biol. Chem., October 13, 2006; 281(41): 31012 - 31020. [Abstract] [Full Text] [PDF]

				R. Ensenauer, M. He, J.-M. Willard, E. S. Goetzman, T. J. Corydon, B. B. Vandahl, A.-W. Mohsen, G. Isaya, and J. Vockley Human Acyl-CoA Dehydrogenase-9 Plays a Novel Role in the Mitochondrial {beta}-Oxidation of Unsaturated Fatty Acids J. Biol. Chem., September 16, 2005; 280(37): 32309 - 32316. [Abstract] [Full Text] [PDF]

				H. S. Toogood, A. van Thiel, N. S. Scrutton, and D. Leys Stabilization of Non-productive Conformations Underpins Rapid Electron Transfer to Electron-transferring Flavoprotein J. Biol. Chem., August 26, 2005; 280(34): 30361 - 30366. [Abstract] [Full Text] [PDF]