4NEE

crystal structure of AP-2 alpha/simga2 complex bound to HIV-1 Nef

Summary for 4NEE

• Entry DOI: 10.2210/pdb4nee/pdb
• Descriptor: AP-2 complex subunit sigma, AP-2 complex subunit alpha-2, Protein Nef (3 entities in total)
• Functional Keywords: clathrin adaptor ap-2, hiv-1 nef, cd4 downregulation, viral protein-protein transport complex, viral protein/protein transport
• Biological source: Rattus norvegicus (brown rat,rat,rats); More
• Cellular location: Cell membrane: Q66HM2
• Total number of polymer chains: 12
• Total formula weight: 316395.85

Authors

Hurley, J.H.,Bonifacino, J.S.,Ren, X.,Park, S.Y. (deposition date: 2013-10-29, release date: 2014-01-29, Last modification date: 2023-09-20)

Primary citation

Ren, X.,Park, S.Y.,Bonifacino, J.S.,Hurley, J.H.
How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4.
Elife, 3:e01754-e01754, 2014

PubMed Abstract: The Nef protein of HIV-1 downregulates the cell surface co-receptor CD4 by hijacking the clathrin adaptor complex AP-2. The structural basis for the hijacking of AP-2 by Nef is revealed by a 2.9 Å crystal structure of Nef bound to the α and σ2 subunits of AP-2. Nef binds to AP-2 via its central loop (residues 149-179) and its core. The determinants for Nef binding include residues that directly contact AP-2 and others that stabilize the binding-competent conformation of the central loop. Residues involved in both direct and indirect interactions are required for the binding of Nef to AP-2 and for downregulation of CD4. These results lead to a model for the docking of the full AP-2 tetramer to membranes as bound to Nef, such that the cytosolic tail of CD4 is situated to interact with its binding site on Nef. DOI: http://dx.doi.org/10.7554/eLife.01754.001.

PubMed: 24473078
DOI: 10.7554/eLife.01754

Experimental method

X-RAY DIFFRACTION (2.8841 Å)