Opening of the ADP-bound active site in the ABC transporter ATPase dimer: Evidence for a constant contact, alternating sites model for the catalytic cycle

Jones, PM; George, AM

Opening of the ADP-bound active site in the ABC transporter ATPase dimer: Evidence for a constant contact, alternating sites model for the catalytic cycle

Jones, PM George, AM

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Publication Type:: Journal Article
Citation:: Proteins: Structure, Function and Bioinformatics, 2009, 75 (2), pp. 387 - 396
Issue Date:: 2009-05-01

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Field	Value	Language
dc.contributor.author	Jones, PM	en_US
dc.contributor.author	George, AM https://orcid.org/0000-0003-4691-8960	en_US
dc.date.issued	2009-05-01	en_US
dc.identifier.citation	Proteins: Structure, Function and Bioinformatics, 2009, 75 (2), pp. 387 - 396	en_US
dc.identifier.issn	0887-3585	en_US
dc.identifier.uri	http://hdl.handle.net/10453/8702
dc.description.abstract	ABC transporters are ubiquitous, ATP-dependent transmembrane pumps. The mechanism by which ATP hydrolysis in the nucleotide-binding domain (NBD) effects conformational changes in the transmembrane domain that lead to allocrite translocation remains largely unknown. A possible aspect of this mechanism was suggested by previous molecular dynamics simulations of the MJ0796 NBD dimer, which revealed a novel, nucleotide-dependent intrasubunit conformational change involving the relative rotation of the helical and catalytic subdomains. Here, we find that in four of five simulations of the ADP/ATP-bound dimer, the relative rotation of the helical and catalytic subdomains in the ADP-bound monomer results in opening of the ADP-bound active site, probably sufficient or close to sufficient to allow nucleotide exchange. We also observe that in all five simulations of the ADP/ ATP-bound dimer, the intimate contact of the LSGGQ signature sequence with the ATP y-phosphate is weakened by the intrasubunit conformational change within the ADP-bound monomer. We discuss how these results support a constant contact model for the function of the NBD dimer in contrast to switch models, in which the NBDs are proposed to fully disassociate during the catalytic cycle. © 2008 wiley-Liss, inc.	en_US
dc.relation.ispartof	Proteins: Structure, Function and Bioinformatics	en_US
dc.relation.isbasedon	10.1002/prot.22250	en_US
dc.subject.classification	Bioinformatics	en_US
dc.subject.mesh	ATP-Binding Cassette Transporters	en_US
dc.subject.mesh	Adenosine Diphosphate	en_US
dc.subject.mesh	Adenosine Triphosphate	en_US
dc.subject.mesh	Crystallography, X-Ray	en_US
dc.subject.mesh	Catalytic Domain	en_US
dc.subject.mesh	Protein Conformation	en_US
dc.subject.mesh	Protein Structure, Tertiary	en_US
dc.subject.mesh	Protein Binding	en_US
dc.subject.mesh	Models, Molecular	en_US
dc.subject.mesh	Computer Simulation	en_US
dc.subject.mesh	Protein Multimerization	en_US
dc.title	Opening of the ADP-bound active site in the ABC transporter ATPase dimer: Evidence for a constant contact, alternating sites model for the catalytic cycle	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	75	en_US
utslib.for	060102 Bioinformatics	en_US
utslib.for	01 Mathematical Sciences	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	08 Information and Computing Sciences	en_US
dc.location.activity	ISI:000264169400011	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	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	75	en_US

Abstract:

ABC transporters are ubiquitous, ATP-dependent transmembrane pumps. The mechanism by which ATP hydrolysis in the nucleotide-binding domain (NBD) effects conformational changes in the transmembrane domain that lead to allocrite translocation remains largely unknown. A possible aspect of this mechanism was suggested by previous molecular dynamics simulations of the MJ0796 NBD dimer, which revealed a novel, nucleotide-dependent intrasubunit conformational change involving the relative rotation of the helical and catalytic subdomains. Here, we find that in four of five simulations of the ADP/ATP-bound dimer, the relative rotation of the helical and catalytic subdomains in the ADP-bound monomer results in opening of the ADP-bound active site, probably sufficient or close to sufficient to allow nucleotide exchange. We also observe that in all five simulations of the ADP/ ATP-bound dimer, the intimate contact of the LSGGQ signature sequence with the ATP y-phosphate is weakened by the intrasubunit conformational change within the ADP-bound monomer. We discuss how these results support a constant contact model for the function of the NBD dimer in contrast to switch models, in which the NBDs are proposed to fully disassociate during the catalytic cycle. © 2008 wiley-Liss, inc.

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http://hdl.handle.net/10453/8702