7Z5C

Chimera of AP2 with FCHO2 linker domain as a fusion on Cmu2 subunit

7Z5C の概要

• エントリーDOI: 10.2210/pdb7z5c/pdb
• EMDBエントリー: 14517
• 分子名称: AP-2 complex subunit alpha-2, AP-2 complex subunit beta, AP-2 complex subunit mu, ... (4 entities in total)
• 機能のキーワード: adaptor complex, ap2, trafficking, clathrin, ccp, protein transport
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 203374.82

構造登録者

Kane Dickson, V.,Qu, K.,Owen, D.J.,Briggs, J.A.,Zaccai, N.R. (登録日: 2022-03-09, 公開日: 2022-05-11, 最終更新日: 2025-07-02)

主引用文献

Zaccai, N.R.,Kadlecova, Z.,Dickson, V.K.,Korobchevskaya, K.,Kamenicky, J.,Kovtun, O.,Umasankar, P.K.,Wrobel, A.G.,Kaufman, J.G.G.,Gray, S.R.,Qu, K.,Evans, P.R.,Fritzsche, M.,Sroubek, F.,Honing, S.,Briggs, J.A.G.,Kelly, B.T.,Owen, D.J.,Traub, L.M.
FCHO controls AP2's initiating role in endocytosis through a PtdIns(4,5)P 2 -dependent switch.
Sci Adv, 8:eabn2018-eabn2018, 2022

PubMed Abstract: Clathrin-mediated endocytosis (CME) is the main mechanism by which mammalian cells control their cell surface proteome. Proper operation of the pivotal CME cargo adaptor AP2 requires membrane-localized Fer/Cip4 homology domain-only proteins (FCHO). Here, live-cell enhanced total internal reflection fluorescence-structured illumination microscopy shows that FCHO marks sites of clathrin-coated pit (CCP) initiation, which mature into uniform-sized CCPs comprising a central patch of AP2 and clathrin corralled by an FCHO/Epidermal growth factor potential receptor substrate number 15 (Eps15) ring. We dissect the network of interactions between the FCHO interdomain linker and AP2, which concentrates, orients, tethers, and partially destabilizes closed AP2 at the plasma membrane. AP2's subsequent membrane deposition drives its opening, which triggers FCHO displacement through steric competition with phosphatidylinositol 4,5-bisphosphate, clathrin, cargo, and CME accessory factors. FCHO can now relocate toward a CCP's outer edge to engage and activate further AP2s to drive CCP growth/maturation.

PubMed: 35486718
DOI: 10.1126/sciadv.abn2018

実験手法

ELECTRON MICROSCOPY (4.16 Å)