2W6A

X-ray Structure of the Dimeric GIT1 Coiled-Coil Domain

2W6A の概要

• エントリーDOI: 10.2210/pdb2w6a/pdb
• 分子名称: ARF GTPASE-ACTIVATING PROTEIN GIT1 (2 entities in total)
• 機能のキーワード: git, arf, pix, zinc, arf6, git1, signaling protein, cat-1, cytoplasm, ank repeat, coiled-coil, zinc-finger, metal-binding, phosphoprotein, gtpase activation
• 由来する生物種: RATTUS NORVEGICUS (RAT)
• 細胞内の位置: Cytoplasm (By similarity): Q9Z272
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 14082.10

構造登録者

Schlenker, O.,Rittinger, K. (登録日: 2008-12-17, 公開日: 2009-01-20, 最終更新日: 2024-05-08)

主引用文献

Schlenker, O.,Rittinger, K.
Structures of Dimeric Git1 and Trimeric Beta-Pix and Implications for Git-Pix Complex Assembly.
J.Mol.Biol., 386:280-, 2009

PubMed Abstract: GIT (G protein-coupled receptor kinase-interacting protein) and PIX (p21-activated kinase-interacting exchange factor) family proteins integrate signaling pathways involving Arf and Rho family GTPases. GIT1 and beta-PIX form a constitutively associated complex that acts as a scaffold to allow the formation of large multiprotein assemblies that regulate synaptogenesis, cell polarity and cell migration among other physiological processes. Complex formation is mediated by the GIT binding domain (GBD) in beta-PIX, which recognizes the Spa homology domain of GIT1. Both binding domains are adjacent to predicted coiled-coil segments that allow homo-oligomerization of GIT1 and beta-PIX, respectively. Oligomerization of GIT and PIX proteins is important for their physiological functions, and deletion of the coiled-coil domains interferes with correct subcellular localization and the GEF (guanine nucleotide exchange factor) activity of PIX. We have solved the crystal structures of the CC domains of GIT1 and beta-PIX and determined the stoichiometry of complex formation between the two proteins in order to understand the molecular architecture of the GIT1-beta-PIX complex. The crystal structure of the CC domain of GIT1 solved at 1.4 A resolution shows a dimeric, parallel CC that spans 67 A in length. Unexpectedly, and in contrast to prevalent dimeric models, the structure of the CC region of beta-PIX determined at 2.8 A resolution, combined with hydrodynamic studies, reveals that this protein forms a parallel trimer. Furthermore, we demonstrate that dimeric GIT and trimeric PIX form an unusual high-affinity heteropentameric complex in which each Spa homology domain of the GIT1 dimer recognizes one GBD of the beta-PIX trimer, leaving one GBD unoccupied. These results can serve as a basis to better understand oligomerization-dependent GIT1-beta-PIX-regulated signaling events and provide an insight into the architecture of large signaling complexes involving GIT1 and beta-PIX.

PubMed: 19136011
DOI: 10.1016/J.JMB.2008.12.050

実験手法

X-RAY DIFFRACTION (1.4 Å)