7OI5

Crystal structure of AP2 Mu2 - FCHO2 chimera (GST cleaved)

Summary for 7OI5

• Entry DOI: 10.2210/pdb7oi5/pdb
• Descriptor: AP-2 complex subunit mu,F-BAR domain only protein 2, GLYCEROL (3 entities in total)
• Functional Keywords: clathrin-mediated endocytosis (cme), protein recycling, plasma membrane, endocytosis
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 2
• Total formula weight: 79025.94

Authors

Zaccai, N.R.,Kelly, B.T.,Evans, P.R.,Owen, D.J. (deposition date: 2021-05-11, release date: 2022-06-01, Last modification date: 2024-06-19)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.61 Å)