1xa6
Crystal Structure of the Human Beta2-Chimaerin
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OverviewOverview
The lipid second messenger diacylglycerol acts by binding to the C1, domains of target proteins, which translocate to cell membranes and are, allosterically activated. Here we report the crystal structure at 3.2 A, resolution of one such protein, beta2-chimaerin, a GTPase-activating, protein for the small GTPase Rac, in its inactive conformation. The, structure shows that in the inactive state, the N terminus of, beta2-chimaerin protrudes into the active site of the RacGAP domain, sterically blocking Rac binding. The diacylglycerol and phospholipid, membrane binding site on the C1 domain is buried by contacts with the four, different regions of beta2-chimaerin: the N terminus, SH2 domain, RacGAP, domain, and the linker between the SH2 and C1 domains. Phospholipid, binding to the C1 domain triggers the cooperative dissociation of these, interactions, allowing the N terminus to move out of the active site and, thereby activating the enzyme.
DiseaseDisease
Known disease associated with this structure: Apnea, postanesthetic OMIM:[177400]
About this StructureAbout this Structure
1XA6 is a Single protein structure of sequence from Homo sapiens with ZN as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural mechanism for lipid activation of the Rac-specific GAP, beta2-chimaerin., Canagarajah B, Leskow FC, Ho JY, Mischak H, Saidi LF, Kazanietz MG, Hurley JH, Cell. 2004 Oct 29;119(3):407-18. PMID:15507211
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