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How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4

  • Author(s): Ren, X
  • Park, SY
  • Bonifacino, JS
  • Hurley, JH
  • et al.

Published Web Location

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901399/
No data is associated with this publication.
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.

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