1I49

CRYSTAL STRUCTURE ANALYSIS OF ARFAPTIN

1I49 の概要

• エントリーDOI: 10.2210/pdb1i49/pdb
• 分子名称: ARFAPTIN 2 (2 entities in total)
• 機能のキーワード: signaling protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51228.11

構造登録者

Tarricone, C.,Xiao, B.,Justin, N.,Gamblin, S.J.,Smerdon, S.J. (登録日: 2001-02-20, 公開日: 2001-05-16, 最終更新日: 2024-02-07)

主引用文献

Tarricone, C.,Xiao, B.,Justin, N.,Walker, P.A.,Rittinger, K.,Gamblin, S.J.,Smerdon, S.J.
The structural basis of Arfaptin-mediated cross-talk between Rac and Arf signalling pathways.
Nature, 411:215-219, 2001

PubMed Abstract: Small G proteins are GTP-dependent molecular switches that regulate numerous cellular functions. They can be classified into homologous subfamilies that are broadly associated with specific biological processes. Cross-talk between small G-protein families has an important role in signalling, but the mechanism by which it occurs is poorly understood. The coordinated action of Arf and Rho family GTPases is required to regulate many cellular processes including lipid signalling, cell motility and Golgi function. Arfaptin is a ubiquitously expressed protein implicated in mediating cross-talk between Rac (a member of the Rho family) and Arf small GTPases. Here we show that Arfaptin binds specifically to GTP-bound Arf1 and Arf6, but binds to Rac.GTP and Rac.GDP with similar affinities. The X-ray structure of Arfaptin reveals an elongated, crescent-shaped dimer of three-helix coiled-coils. Structures of Arfaptin with Rac bound to either GDP or the slowly hydrolysable analogue GMPPNP show that the switch regions adopt similar conformations in both complexes. Our data highlight fundamental differences between the molecular mechanisms of Rho and Ras family signalling, and suggest a model of Arfaptin-mediated synergy between the Arf and Rho family signalling pathways.

PubMed: 11346801
DOI: 10.1038/35075620

実験手法

X-RAY DIFFRACTION (2.8 Å)