4C4P

Crystal Structure of Wild-Type Rab11 Complexed to FIP2

4C4P の概要

• エントリーDOI: 10.2210/pdb4c4p/pdb
• 分子名称: RAS-RELATED PROTEIN RAB-11A, RAB11 FAMILY-INTERACTING PROTEIN 2, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (5 entities in total)
• 機能のキーワード: protein transport, effector, vesicle trafficking, endosomes
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Cell membrane; Peripheral membrane protein: P62491 Q7L804
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32352.32

構造登録者

Sultana, A.,Khan, A.R. (登録日: 2013-09-07, 公開日: 2013-09-18, 最終更新日: 2024-05-08)

主引用文献

Lall, P.,Horgan, C.P.,Oda, S.,Franklin, E.,Sultana, A.,Hanscomb, S.R.,Mccaffrey, M.W.,Khan, A.R.
Structural and Functional Analysis of Fip2 Binding to the Endosome-Localised Rab25 Gtpase
Biochim.Biophys.Acta, 1834:2679-, 2013

PubMed Abstract: Rab small GTPases are the master regulators of intracellular trafficking in eukaryotes. They mediate spatial and temporal recruitment of effector proteins to distinct cellular compartments through GTP-induced changes in their conformation. Despite numerous structural studies, the molecular basis for Rab/effector specificity and subsequent biological activity remains poorly understood. Rab25, also known as Rab11c, which is epithelial-specific, has been heavily implicated in ovarian cancer development and independently appears to act as a tumour suppressor in the context of a distinct subset of carcinomas. Here, we show that Rab25 associates with FIP2 and can recruit this effector protein to endosomal membranes. We report the crystal structure of Rab25 in complex with the C-terminal region of FIP2, which consists of a central dimeric FIP2 coiled-coil that mediates a heterotetrameric Rab25-(FIP2)2-Rab25 complex. Thermodynamic analyses show that, despite a relatively conserved interface, FIP2 binds to Rab25 with an approximate 3-fold weaker affinity than to Rab11a. Reduced affinity is mainly associated with lower enthalpic gains for Rab25:FIP2 complex formation, and can be attributed to subtle differences in the conformations of switch 1 and switch 2. These cellular, structural and thermodynamic studies provide insight into the Rab11/Rab25 subfamily of small GTPases that regulate endosomal trafficking pathways in eukaryotes.

PubMed: 24056041
DOI: 10.1016/J.BBAPAP.2013.09.005

実験手法

X-RAY DIFFRACTION (2 Å)