Perspectives on the structure-function of ABC transporters: The Switch and Constant Contact Models

George, AM; Jones, PM

Perspectives on the structure-function of ABC transporters: The Switch and Constant Contact Models

George, AM

Jones, PM

Permalink

Publication Type:: Journal Article
Citation:: Progress in Biophysics and Molecular Biology, 2012, 109 (3), pp. 95 - 107
Issue Date:: 2012-08-01

Closed Access

	Filename	Description	Size
	2011005741OK.pdf		686.51 kB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	George, AM https://orcid.org/0000-0003-4691-8960	en_US
dc.contributor.author	Jones, PM	en_US
dc.date.available	2012-06-14	en_US
dc.date.issued	2012-08-01	en_US
dc.identifier.citation	Progress in Biophysics and Molecular Biology, 2012, 109 (3), pp. 95 - 107	en_US
dc.identifier.issn	0079-6107	en_US
dc.identifier.uri	http://hdl.handle.net/10453/22143
dc.description.abstract	ABC transporters constitute one of the largest protein families across the kingdoms of archaea, eubacteria and eukarya. They couple ATP hydrolysis to vectorial translocation of diverse substrates across membranes. The ABC transporter architecture comprises two transmembrane domains and two cytosolic ATP-binding cassettes. During 2002-2012, nine prokaryotic ABC transporter structures and two eukaryotic structures have been solved to medium resolution. Despite a wealth of biochemical, biophysical, and structural data, fundamental questions remain regarding the coupling of ATP hydrolysis to unidirectional substrate translocation, and the mechanistic suite of steps involved. The mechanics of the ATP cassette dimer is defined most popularly by the 'Switch Model', which proposes that hydrolysis in each protomer is sequential, and that as the sites are freed of nucleotide, the protomers lose contact across a large solvent-filled gap of 20-30 å; as captured in several X-ray solved structures. Our 'Constant Contact' model for the operational mechanics of ATP binding and hydrolysis in the ATP-binding cassettes is derived from the 'alternating sites' model, proposed in 1995, and which requires an intrinsic asymmetry in the ATP sites, but does not require the partner protomers to lose contact. Thus one of the most debated issues regarding the function of ABC transporters is whether the cooperative mechanics of ATP hydrolysis requires the ATP cassettes to separate or remain in constant contact and this dilemma is discussed at length in this review. © 2012 Elsevier Ltd.	en_US
dc.relation.ispartof	Progress in Biophysics and Molecular Biology	en_US
dc.relation.isbasedon	10.1016/j.pbiomolbio.2012.06.003	en_US
dc.subject.classification	Biophysics	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	ATP-Binding Cassette Transporters	en_US
dc.subject.mesh	Adenosine Triphosphate	en_US
dc.subject.mesh	Protein Structure, Tertiary	en_US
dc.subject.mesh	Structure-Activity Relationship	en_US
dc.subject.mesh	Models, Molecular	en_US
dc.subject.mesh	Biocatalysis	en_US
dc.title	Perspectives on the structure-function of ABC transporters: The Switch and Constant Contact Models	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	109	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	109	en_US

Abstract:

ABC transporters constitute one of the largest protein families across the kingdoms of archaea, eubacteria and eukarya. They couple ATP hydrolysis to vectorial translocation of diverse substrates across membranes. The ABC transporter architecture comprises two transmembrane domains and two cytosolic ATP-binding cassettes. During 2002-2012, nine prokaryotic ABC transporter structures and two eukaryotic structures have been solved to medium resolution. Despite a wealth of biochemical, biophysical, and structural data, fundamental questions remain regarding the coupling of ATP hydrolysis to unidirectional substrate translocation, and the mechanistic suite of steps involved. The mechanics of the ATP cassette dimer is defined most popularly by the 'Switch Model', which proposes that hydrolysis in each protomer is sequential, and that as the sites are freed of nucleotide, the protomers lose contact across a large solvent-filled gap of 20-30 å; as captured in several X-ray solved structures. Our 'Constant Contact' model for the operational mechanics of ATP binding and hydrolysis in the ATP-binding cassettes is derived from the 'alternating sites' model, proposed in 1995, and which requires an intrinsic asymmetry in the ATP sites, but does not require the partner protomers to lose contact. Thus one of the most debated issues regarding the function of ABC transporters is whether the cooperative mechanics of ATP hydrolysis requires the ATP cassettes to separate or remain in constant contact and this dilemma is discussed at length in this review. © 2012 Elsevier Ltd.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/22143