6GBU

Crystal structure of the second SH3 domain of FCHSD2 (SH3-2) in complex with the fourth SH3 domain of ITSN1 (SH3d)

6GBU の概要

• エントリーDOI: 10.2210/pdb6gbu/pdb
• 分子名称: F-BAR and double SH3 domains protein 2, Intersectin-1 (2 entities in total)
• 機能のキーワード: sh3-sh3 complex, endocytosis
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 57208.49

構造登録者

Almeida-Souza, L.,Frank, R.,Garcia-Nafria, J.,Colussi, A.,Gunawardana, N.,Johnson, C.M.,Yu, M.,Howard, G.,Andrews, B.,Vallis, Y.,McMahon, H.T. (登録日: 2018-04-16, 公開日: 2018-06-13, 最終更新日: 2024-10-23)

主引用文献

Almeida-Souza, L.,Frank, R.A.W.,Garcia-Nafria, J.,Colussi, A.,Gunawardana, N.,Johnson, C.M.,Yu, M.,Howard, G.,Andrews, B.,Vallis, Y.,McMahon, H.T.
A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits.
Cell, 174:325-337.e14, 2018

PubMed Abstract: Multiple proteins act co-operatively in mammalian clathrin-mediated endocytosis (CME) to generate endocytic vesicles from the plasma membrane. The principles controlling the activation and organization of the actin cytoskeleton during mammalian CME are, however, not fully understood. Here, we show that the protein FCHSD2 is a major activator of actin polymerization during CME. FCHSD2 deletion leads to decreased ligand uptake caused by slowed pit maturation. FCHSD2 is recruited to endocytic pits by the scaffold protein intersectin via an unusual SH3-SH3 interaction. Here, its flat F-BAR domain binds to the planar region of the plasma membrane surrounding the developing pit forming an annulus. When bound to the membrane, FCHSD2 activates actin polymerization by a mechanism that combines oligomerization and recruitment of N-WASP to PI(4,5)P, thus promoting pit maturation. Our data therefore describe a molecular mechanism for linking spatiotemporally the plasma membrane to a force-generating actin platform guiding endocytic vesicle maturation.

PubMed: 29887380
DOI: 10.1016/j.cell.2018.05.020

実験手法

X-RAY DIFFRACTION (3.44 Å)