Structural highlights
Function
[ASAP3_HUMAN] Promotes cell proliferation.[1]
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
Arfs are small G proteins that have a key role in vesicle trafficking and cytoskeletal remodeling. ArfGAP proteins stimulate Arf intrinsic GTP hydrolysis by a mechanism that is still unresolved. Using a fusion construct we solved the structure of the ArfGAP ASAP3 in complex with Arf6 in the transition state. This structure clarifies the ArfGAP catalytic mechanism and shows a glutamine((Arf6)) and an arginine finger((ASAP3)) as the important catalytic residues. Unexpectedly the structure shows a calcium ion, liganded by both proteins in the complex interface, stabilizing the interaction and orienting the catalytic machinery. Calcium stimulates the GAP activity of ASAPs, but not other members of the ArfGAP family. This type of regulation is unique for GAPs and any other calcium-regulated processes and hints at a crosstalk between Ca(2+) and Arf signaling.
The structure of an Arf-ArfGAP complex reveals a Ca2+ regulatory mechanism.,Ismail SA, Vetter IR, Sot B, Wittinghofer A Cell. 2010 May 28;141(5):812-21. PMID:20510928[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Okabe H, Furukawa Y, Kato T, Hasegawa S, Yamaoka Y, Nakamura Y. Isolation of development and differentiation enhancing factor-like 1 (DDEFL1) as a drug target for hepatocellular carcinomas. Int J Oncol. 2004 Jan;24(1):43-8. PMID:14654939
- ↑ Ismail SA, Vetter IR, Sot B, Wittinghofer A. The structure of an Arf-ArfGAP complex reveals a Ca2+ regulatory mechanism. Cell. 2010 May 28;141(5):812-21. PMID:20510928 doi:10.1016/j.cell.2010.03.051
