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-Structure paper
タイトル | FCHO controls AP2's initiating role in endocytosis through a PtdIns(4,5)P-dependent switch. |
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ジャーナル・号・ページ | Sci Adv, Vol. 8, Issue 17, Page eabn2018, Year 2022 |
掲載日 | 2022年4月29日 |
![]() | Nathan R Zaccai / Zuzana Kadlecova / Veronica Kane Dickson / Kseniya Korobchevskaya / Jan Kamenicky / Oleksiy Kovtun / Perunthottathu K Umasankar / Antoni G Wrobel / Jonathan G G Kaufman / Sally R Gray / Kun Qu / Philip R Evans / Marco Fritzsche / Filip Sroubek / Stefan Höning / John A G Briggs / Bernard T Kelly / David J Owen / Linton M Traub / ![]() ![]() ![]() ![]() ![]() |
PubMed 要旨 | 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- ...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. |
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手法 | EM (単粒子) / EM (トモグラフィー) / EM (サブトモグラム平均) / X線回折 |
解像度 | 1.41 - 12.0 Å |
構造データ | EMDB-14517: Chimaera of AP2 with FCHO2 linker domain as a fusion on Cmu2 subunit ![]() EMDB-14518: Chimaera of AP2 with FCHO2 linker domain, N1-N2 enriched population ![]() EMDB-14525: AP2 adaptor protein recruited on the membrane in the presence of FCHO2 linker ![]() EMDB-14526: AP2 on the membrane without cargo peptide ![]() PDB-7ofp: ![]() PDB-7og1: ![]() PDB-7ohi: ![]() PDB-7oho: ![]() PDB-7ohz: ![]() PDB-7oi5: ![]() PDB-7oiq: ![]() PDB-7oit: |
化合物 | ![]() ChemComp-GOL: ![]() ChemComp-CIT: ![]() ChemComp-HOH: ![]() ChemComp-SO4: ![]() ChemComp-MES: ![]() ChemComp-IHP: |
由来 |
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![]() | ENDOCYTOSIS / clathrin-mediated endocytosis (CME) / YxxPhi motif / Pi(4 / 5)P2 / protein recycling / plasma membrane / PROTEIN TRANSPORT / adaptor complex / AP2 / trafficking / clathrin / CCP |