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AP2 controls clathrin polymerization with a membrane-activated switch

DOI: 10.1126/science.1254836 DOI Help
PMID: 25061211 PMID Help

Authors: Bernie Kelly (Cambridge Institute for Medical Research (CIMR), Department of Clinical Biochemistry, University of Cambridge, U.K.) , S. C. Graham (Department of Pathology, University of Cambridge, U.K.) , N. Liska (Cambridge Institute for Medical Research (CIMR), Department of Clinical Biochemistry, University of Cambridge, U.K.) , P. N. Dannhauser (Department of Cell Biology, Center of Anatomy, Hannover Medical School,Germany) , S. Honing (Institute of Biochemistry I and Center for Molecular Medicine Cologne, University of Cologne, Germany) , E. J. Ungewickell (Department of Cell Biology, Center of Anatomy, Hannover Medical School,Germany) , David Owen (Cambridge Institute for Medical Research (CIMR), Department of Clinical Biochemistry, University of Cambridge, U.K.)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science , VOL 345 (6195) , PAGES 459 - 463

State: Published (Approved)
Published: July 2014
Diamond Proposal Number(s): 8547

Abstract: Clathrin-mediated endocytosis (CME) is vital for the internalization of most cell-surface proteins. In CME, plasma membrane¬Ėbinding clathrin adaptors recruit and polymerize clathrin to form clathrin-coated pits into which cargo is sorted. Assembly polypeptide 2 (AP2) is the most abundant adaptor and is pivotal to CME. Here, we determined a structure of AP2 that includes the clathrin-binding β2 hinge and developed an AP2-dependent budding assay. Our findings suggest that an autoinhibitory mechanism prevents clathrin recruitment by cytosolic AP2. A large-scale conformational change driven by the plasma membrane phosphoinositide phosphatidylinositol 4,5-bisphosphate and cargo relieves this autoinhibition, triggering clathrin recruitment and hence clathrin-coated bud formation. This molecular switching mechanism can couple AP2¬ís membrane recruitment to its key functions of cargo and clathrin binding.

Journal Keywords: Adaptor; Cell; Clathrin ; Endocytosis ; Humans ; Phosphatidylinositol; Polymerization

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

Other Facilities: No

Added On: 24/09/2014 16:52

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