2XA7

AP2 clathrin adaptor core in active complex with cargo peptides

Summary for 2XA7

• Entry DOI: 10.2210/pdb2xa7/pdb
• Related: 1BW8 1BXX 1E42 1HES 1I31 2BP5 2G30 2IV8 2IV9 2JKR 2JKT 2VGL 2XA8
• Descriptor: ADAPTOR-RELATED PROTEIN COMPLEX 2, ALPHA 2 SUBUNIT, AP-2 COMPLEX SUBUNIT BETA, AP-2 COMPLEX SUBUNIT MU,, ... (6 entities in total)
• Functional Keywords: phosphoprotein, protein transport, endocytosis, cell membrane, lipid-binding
• Biological source: RATTUS NORVEGICUS (RAT); More
• Cellular location: Cell membrane: P63010 P62743; Cell membrane (By similarity): P84092
• Total number of polymer chains: 5
• Total formula weight: 206119.62

Authors

Jackson, L.P.,Kelly, B.T.,McCoy, A.J.,Evans, P.R.,Owen, D.J. (deposition date: 2010-03-29, release date: 2010-07-21, Last modification date: 2024-05-08)

Primary citation

Jackson, L.P.,Kelly, B.T.,Mccoy, A.J.,Gaffry, T.,James, L.C.,Collins, B.M.,Honing, S.,Evans, P.R.,Owen, D.J.
A Large Scale Conformational Change Couples Membrane Recruitment to Cargo Binding in the Ap2 Clathrin Adaptor Complex
Cell(Cambridge,Mass.), 141:1241-, 2010

PubMed Abstract: The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Using protein crystallography, we show that AP2 undergoes a large conformational change in which C-mu2 relocates to an orthogonal face of the complex, simultaneously unblocking both cargo-binding sites; the previously unstructured mu2 linker becomes helical and binds back onto the complex. This structural rearrangement results in AP2's four PtdIns4,5P(2)- and two endocytic motif-binding sites becoming coplanar, facilitating their simultaneous interaction with PtdIns4,5P(2)/cargo-containing membranes. Using a range of biophysical techniques, we show that the endocytic cargo binding of AP2 is driven by its interaction with PtdIns4,5P(2)-containing membranes.

PubMed: 20603002
DOI: 10.1016/J.CELL.2010.05.005

Experimental method

X-RAY DIFFRACTION (3.1 Å)