4NEE: Crystal Structure Of Ap-2 Alpha/simga2 Complex Bound To Hiv-1 Nef

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 A crystal structure of Nef bound to the alpha and sigma2 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.
PDB ID: 4NEEDownload
MMDB ID: 117090
PDB Deposition Date: 2013/10/29
Updated in MMDB: 2014/03
Experimental Method:
x-ray diffraction
Resolution: 2.88  Å
Source Organism:
Human immunodeficiency virus 1
Similar Structures:
Biological Unit for 4NEE: trimeric; determined by author and by software (PISA)
Molecular Components in 4NEE
Label Count Molecule
Proteins (3 molecules)
Ap-2 Complex Subunit Sigma(Gene symbol: Ap2s1)
Molecule annotation
Ap-2 Complex Subunit Alpha-2
Molecule annotation
Protein NEF
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB