| Structural highlights
Function
[RHG21_HUMAN] Functions as a GTPase-activating protein (GAP) for RHOA and CDC42. Downstream partner of ARF1 which may control Golgi apparatus structure and function. Also required for CTNNA1 recruitment to adherens junctions.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
ARHGAP21 is a Rho family GTPase-activating protein (RhoGAP) that controls the Arp2/3 complex and F-actin dynamics at the Golgi complex by regulating the activity of the small GTPase Cdc42. ARHGAP21 is recruited to the Golgi by binding to another small GTPase, ARF1. Here, we present the crystal structure of the activated GTP-bound form of ARF1 in a complex with the Arf-binding domain (ArfBD) of ARHGAP21 at 2.1 A resolution. We show that ArfBD comprises a PH domain adjoining a C-terminal alpha helix, and that ARF1 interacts with both of these structural motifs through its switch regions and triggers structural rearrangement of the PH domain. We used site-directed mutagenesis to confirm that both the PH domain and the helical motif are essential for the binding of ArfBD to ARF1 and for its recruitment to the Golgi. Our data demonstrate that two well-known small GTPase-binding motifs, the PH domain and the alpha helical motif, can combine to create a novel mode of binding to Arfs.
Structural basis for ARF1-mediated recruitment of ARHGAP21 to Golgi membranes.,Menetrey J, Perderiset M, Cicolari J, Dubois T, Elkhatib N, El Khadali F, Franco M, Chavrier P, Houdusse A EMBO J. 2007 Apr 4;26(7):1953-62. Epub 2007 Mar 8. PMID:17347647[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dubois T, Paleotti O, Mironov AA, Fraisier V, Stradal TE, De Matteis MA, Franco M, Chavrier P. Golgi-localized GAP for Cdc42 functions downstream of ARF1 to control Arp2/3 complex and F-actin dynamics. Nat Cell Biol. 2005 Apr;7(4):353-64. Epub 2005 Mar 27. PMID:15793564 doi:http://dx.doi.org/10.1038/ncb1244
- ↑ Sousa S, Cabanes D, Archambaud C, Colland F, Lemichez E, Popoff M, Boisson-Dupuis S, Gouin E, Lecuit M, Legrain P, Cossart P. ARHGAP10 is necessary for alpha-catenin recruitment at adherens junctions and for Listeria invasion. Nat Cell Biol. 2005 Oct;7(10):954-60. Epub 2005 Sep 25. PMID:16184169 doi:http://dx.doi.org/ncb1308
- ↑ Menetrey J, Perderiset M, Cicolari J, Dubois T, Elkhatib N, El Khadali F, Franco M, Chavrier P, Houdusse A. Structural basis for ARF1-mediated recruitment of ARHGAP21 to Golgi membranes. EMBO J. 2007 Apr 4;26(7):1953-62. Epub 2007 Mar 8. PMID:17347647
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