The Structure of an Arf-ArfGAP Complex Reveals a Ca2+ Regulatory Mechanism
The Structure of an Arf-ArfGAP Complex Reveals a Ca2+ Regulatory Mechanism
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DOI：
10.1016/j.cell.2010.03.051
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发表时间：
2010-05-28
期刊：
影响因子：
64.5
通讯作者：
Wittinghofer, Alfred
中科院分区：
文献类型：
--
作者：
Ismail, Shehab A.;Vetter, Ingrid R.;Wittinghofer, Alfred
Arfs是小G蛋白，在囊泡运输和细胞骨架重塑中起关键作用。Arf-GAP蛋白刺激Arf的内在GTP水解的机制，仍然是悬而未决的。使用融合构建体，我们解决了与处于过渡态的Arf 6复合的ArfGAP ASAP 3的结构。该结构阐明了ArfGAP催化机制，并显示谷氨酰胺（（Arf 6））和精氨酸指（（ASAP 3））作为重要的催化残基。出乎意料的是，结构显示钙离子，在复杂的界面中被两种蛋白质配体，稳定相互作用并定向催化机制。钙刺激ASAP差距活性，但不刺激ArfGAP家族的其他成员。这种类型的调节对于GAP和任何其他钙调节过程是独特的，并暗示Ca 2+和Arf信号之间的串扰。
Arfs are small G proteins that have a key role in vesicle trafficking and cytoskeletal remodeling. Arf-GAP 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 Ca2+ and Arf signaling.