4kax
From Proteopedia
Crystal structure of the Grp1 PH domain in complex with Arf6-GTP
Structural highlights
Function[ARF6_HUMAN] GTP-binding protein involved in protein trafficking; regulates endocytic recycling and cytoskeleton remodeling. May modulate vesicle budding and uncoating within the Golgi apparatus. Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in the regulation of dendritic spine development (By similarity). Contributes to the regulation of dendritic branching and filopodia extension.[1] [2] [3] [CYH3_HUMAN] Promotes guanine-nucleotide exchange on ARF1. Promotes the activation of ARF through replacement of GDP with GTP. Publication Abstract from PubMedMembrane 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. Structural basis for membrane recruitment and allosteric activation of cytohesin family Arf GTPase exchange factors.,Malaby AW, van den Berg B, Lambright DG Proc Natl Acad Sci U S A. 2013 Aug 12. PMID:23940353[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
