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dc.contributor.authorMalaby, Andrew W.
dc.contributor.authorvan den Berg, Bert
dc.contributor.authorLambright, David G.
dc.date2022-08-11T08:10:18.000
dc.date.accessioned2022-08-23T17:03:21Z
dc.date.available2022-08-23T17:03:21Z
dc.date.issued2013-08-27
dc.date.submitted2014-04-14
dc.identifier.citationMalaby AW, van den Berg B, Lambright DG. Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors. Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):14213-8. doi:10.1073/pnas.1301883110. <a href="http://dx.doi.org/10.1073/pnas.1301883110">Link to article on publisher's site</a>
dc.identifier.issn0027-8424 (Linking)
dc.identifier.doi10.1073/pnas.1301883110
dc.identifier.pmid23940353
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44406
dc.description.abstractMembrane recruitment of cytohesin family Arf guanine nucleotide exchange factors depends on interactions with phosphoinositides and active Arf GTPases that, in turn, relieve autoinhibition of the catalytic Sec7 domain through an unknown structural mechanism. Here, we show that Arf6-GTP relieves autoinhibition by binding to an allosteric site that includes the autoinhibitory elements in addition to the PH domain. The crystal structure of a cytohesin-3 construct encompassing the allosteric site in complex with the head group of phosphatidyl inositol 3,4,5-trisphosphate and N-terminally truncated Arf6-GTP reveals a large conformational rearrangement, whereby autoinhibition can be relieved by competitive sequestration of the autoinhibitory elements in grooves at the Arf6/PH domain interface. Disposition of the known membrane targeting determinants on a common surface is compatible with multivalent membrane docking and subsequent activation of Arf substrates, suggesting a plausible model through which membrane recruitment and allosteric activation could be structurally integrated.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23940353&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1073/pnas.1301883110
dc.subjectADP-Ribosylation Factors
dc.subjectAllosteric Site
dc.subjectCatalytic Domain
dc.subjectGTP Phosphohydrolases
dc.subjectModels, Molecular
dc.subjectProtein Conformation
dc.subjectSurface Plasmon Resonance
dc.subjectBiochemistry
dc.titleStructural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors
dc.typeJournal Article
dc.source.journaltitleProceedings of the National Academy of Sciences of the United States of America
dc.source.volume110
dc.source.issue35
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pmm_pp/14
dc.identifier.contextkey5476844
html.description.abstract<p>Membrane recruitment of cytohesin family Arf guanine nucleotide exchange factors depends on interactions with phosphoinositides and active Arf GTPases that, in turn, relieve autoinhibition of the catalytic Sec7 domain through an unknown structural mechanism. Here, we show that Arf6-GTP relieves autoinhibition by binding to an allosteric site that includes the autoinhibitory elements in addition to the PH domain. The crystal structure of a cytohesin-3 construct encompassing the allosteric site in complex with the head group of phosphatidyl inositol 3,4,5-trisphosphate and N-terminally truncated Arf6-GTP reveals a large conformational rearrangement, whereby autoinhibition can be relieved by competitive sequestration of the autoinhibitory elements in grooves at the Arf6/PH domain interface. Disposition of the known membrane targeting determinants on a common surface is compatible with multivalent membrane docking and subsequent activation of Arf substrates, suggesting a plausible model through which membrane recruitment and allosteric activation could be structurally integrated.</p>
dc.identifier.submissionpathpmm_pp/14
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages14213-8


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