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bioRxiv · 10.1101/2020.01.28.922591

Architecture of the AP2:clathrin coat on the membranes of clathrin-coated vesicles

Kovtun, O.·Kane Dickson, V.·Kelly, B. T.·Owen, D. J.·Briggs, J. A. G.
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Abstract

Clathrin-mediated endocytosis (CME) is crucial for modulating the protein composition of a cells plasma membrane. Clathrin forms a cage-like, polyhedral outer scaffold around a vesicle, to which cargo-selecting clathrin adaptors are attached. AP2 is the key adaptor in CME. Crystallography has shown AP2 to adopt a range of conformations. Here we used cryo-electron microscopy, tomography and subtomogram averaging to determine structures, interactions and arrangements of clathrin and AP2 at the key steps of coat assembly, from AP2 in solution to membrane-assembled clathrin-coated vesicles (CCVs). AP2 binds cargo and PtdIns(4,5)P2-containing membranes via multiple interfaces, undergoing conformational rearrangement from its cytosolic state. The binding mode of AP2 {beta}2-appendage into the clathrin lattice in CCVs and buds implies how the adaptor structurally modulates coat curvature and coat disassembly.

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Kovtun, O., Kane Dickson, V., Kelly, B. T., Owen, D. J., Briggs, J. A. G.. 2020-01-28. Architecture of the AP2:clathrin coat on the membranes of clathrin-coated vesicles. https://doi.org/10.1101/2020.01.28.922591

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