4G55

Clathrin terminal domain complexed with pitstop 2

「2XZH」から置き換えられました

4G55 の概要

• エントリーDOI: 10.2210/pdb4g55/pdb
• 関連するPDBエントリー: 2XZG
• 分子名称: Clathrin heavy chain 1, DIMETHYL SULFOXIDE, ACETATE ION, ... (7 entities in total)
• 機能のキーワード: beta-propeller, endocytosis
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side: Q00610
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42728.82

構造登録者

Bulut, H.,Von Kleist, L.,Saenger, W.,Haucke, V. (登録日: 2012-07-17, 公開日: 2012-08-01, 最終更新日: 2024-02-28)

主引用文献

von Kleist, L.,Stahlschmidt, W.,Bulut, H.,Gromova, K.,Puchkov, D.,Robertson, M.J.,MacGregor, K.A.,Tomilin, N.,Tomlin, N.,Pechstein, A.,Chau, N.,Chircop, M.,Sakoff, J.,von Kries, J.P.,Saenger, W.,Krausslich, H.G.,Shupliakov, O.,Robinson, P.J.,McCluskey, A.,Haucke, V.
Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition.
Cell(Cambridge,Mass.), 146:471-484, 2011

PubMed Abstract: Clathrin-mediated endocytosis (CME) regulates many cell physiological processes such as the internalization of growth factors and receptors, entry of pathogens, and synaptic transmission. Within the endocytic network, clathrin functions as a central organizing platform for coated pit assembly and dissociation via its terminal domain (TD). We report the design and synthesis of two compounds named pitstops that selectively block endocytic ligand association with the clathrin TD as confirmed by X-ray crystallography. Pitstop-induced inhibition of clathrin TD function acutely interferes with receptor-mediated endocytosis, entry of HIV, and synaptic vesicle recycling. Endocytosis inhibition is caused by a dramatic increase in the lifetimes of clathrin coat components, including FCHo, clathrin, and dynamin, suggesting that the clathrin TD regulates coated pit dynamics. Pitstops provide new tools to address clathrin function in cell physiology with potential applications as inhibitors of virus and pathogen entry and as modulators of cell signaling.

PubMed: 21816279
DOI: 10.1016/j.cell.2011.06.025

実験手法

X-RAY DIFFRACTION (1.69 Å)