4UQI

AP2 controls clathrin polymerization with a membrane-activated switch

Summary for 4UQI

• Entry DOI: 10.2210/pdb4uqi/pdb
• Descriptor: AP-2 COMPLEX SUBUNIT ALPHA-2, AP-2 COMPLEX SUBUNIT BETA, AP-2 COMPLEX SUBUNIT MU, ... (7 entities in total)
• Functional Keywords: endocytosis, protein transport, lipid binding
• Biological source: RATTUS NORVEGICUS (NORWAY RAT); More
• Total number of polymer chains: 4
• Total formula weight: 213024.27

Authors

Kelly, B.T.,Graham, S.C.,Liska, N.,Dannhauser, P.N.,Hoening, S.,Ungewickell, E.J.,Owen, D.J. (deposition date: 2014-06-23, release date: 2014-07-30, Last modification date: 2024-01-10)

Primary citation

Kelly, B.T.,Graham, S.C.,Liska, N.,Dannhauser, P.N.,Honing, S.,Ungewickell, E.J.,Owen, D.J.
Clathrin Adaptors. Ap2 Controls Clathrin Polymerization with a Membrane-Activated Switch.
Science, 345:459-, 2014

PubMed Abstract: Clathrin-mediated endocytosis (CME) is vital for the internalization of most cell-surface proteins. In CME, plasma membrane-binding 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's membrane recruitment to its key functions of cargo and clathrin binding.

PubMed: 25061211
DOI: 10.1126/SCIENCE.1254836

Experimental method

X-RAY DIFFRACTION (2.79 Å)