1f7c
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(New page: 200px<br /><applet load="1f7c" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f7c, resolution 2.4Å" /> '''CRYSTAL STRUCTURE OF ...)
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Revision as of 21:17, 24 November 2007
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CRYSTAL STRUCTURE OF THE BH DOMAIN FROM GRAF, THE GTPASE REGULATOR ASSOCIATED WITH FOCAL ADHESION KINASE
Overview
Cellular signaling by small G-proteins is down-regulated by, GTPase-activating proteins (GAPs), which increase the rate of GTP, hydrolysis. The GTPase regulator associated with focal adhesion kinase, (Graf) exhibits GAP activity toward the RhoA and Cdc42 GTPases, but is, only weakly active toward the closely related Rac1. We determined the, crystal structure of a 231-residue fragment of Graf (GrafGAP), a domain, containing the GAP activity, at 2.4-A resolution. The structure clarifies, the boundaries of the functional domain and yields insight to the, mechanism of substrate recognition. Modeling its interaction with, substrate suggested that a favorable interaction with Glu-95 of Cdc42, (Glu-97 of RhoA) would be absent with the corresponding Ala-95 of Rac1., Indeed, GrafGAP activity is diminished approximately 40-fold toward a, Cdc42 E95A mutant, whereas a approximately 10-fold increase is observed, for a Rac1 A95E mutant. The GrafGAP epitope that apparently interacts with, Glu-95(Glu-97) contains Asn-225, which was recently found mutated in some, myeloid leukemia patients. We conclude that position 95 of the GTPase is, an important determinant for GrafGAP specificity in cellular function and, tumor suppression.
About this Structure
1F7C is a Single protein structure of sequence from Gallus gallus. Full crystallographic information is available from OCA.
Reference
Structure of the BH domain from graf and its implications for Rho GTPase recognition., Longenecker KL, Zhang B, Derewenda U, Sheffield PJ, Dauter Z, Parsons JT, Zheng Y, Derewenda ZS, J Biol Chem. 2000 Dec 8;275(49):38605-10. PMID:10982819
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