1T9G

Structure of the human MCAD:ETF complex

Summary for 1T9G

• Entry DOI: 10.2210/pdb1t9g/pdb
• Related: 1EFV 1O94 1UDY
• Descriptor: Acyl-CoA dehydrogenase, medium-chain specific, mitochondrial, Electron transfer flavoprotein alpha-subunit, mitochondrial, Electron transfer flavoprotein beta-subunit, ... (5 entities in total)
• Functional Keywords: electron transfer, protein:protein complex, fatty acid oxidation, human electron transferring flavoprotein, human medium chain acyl coa dehydrogenase, oxidoreductase, electron transport
• Biological source: Homo sapiens (human); More
• Cellular location: Mitochondrion matrix: P11310 P13804 P38117
• Total number of polymer chains: 6
• Total formula weight: 241279.82

Authors

Toogood, H.S.,van Thiel, A.,Basran, J.,Sutcliffe, M.J.,Scrutton, N.S.,Leys, D. (deposition date: 2004-05-17, release date: 2004-06-08, Last modification date: 2024-02-14)

Primary citation

Toogood, H.S.,van Thiel, A.,Basran, J.,Sutcliffe, M.J.,Scrutton, N.S.,Leys, D.
Extensive domain motion and electron transfer in the human electron transferring flavoprotein-medium chain Acyl-CoA dehydrogenase complex
J.Biol.Chem., 279:32904-32912, 2004

PubMed Abstract: 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 Glu(212) and ETF Arg alpha(249) are likely to transiently stabilize productive conformations of the FAD domain leading to enhanced electron transfer rates between both partners.

PubMed: 15159392
DOI: 10.1074/jbc.M404884200

Experimental method

X-RAY DIFFRACTION (2.9 Å)