4P6Z

Crystal structure of the human BST2 cytoplasmic domain and the HIV-1 Vpu cytoplasmic domain bound to the clathrin adaptor protein complex 1 (AP1) core

Summary for 4P6Z

• Entry DOI: 10.2210/pdb4p6z/pdb
• Descriptor: AP-1 complex subunit gamma-1, AP-1 complex subunit sigma-1A, AP-1 complex subunit mu-1, ... (7 entities in total)
• Functional Keywords: bst2, tetherin, vpu, hiv, clathrin, ap1, antiviral, restriction factor, antagonism, protein transport
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 6
• Total formula weight: 216053.86

Authors

Jia, X.,Xiong, Y. (deposition date: 2014-03-25, release date: 2014-05-21, Last modification date: 2023-12-27)

Primary citation

Jia, X.,Weber, E.,Tokarev, A.,Lewinski, M.,Rizk, M.,Suarez, M.,Guatelli, J.,Xiong, Y.
Structural basis of HIV-1 Vpu-mediated BST2 antagonism via hijacking of the clathrin adaptor protein complex 1.
Elife, 3:e02362-e02362, 2014

PubMed Abstract: BST2/tetherin, an antiviral restriction factor, inhibits the release of enveloped viruses from the cell surface. Human immunodeficiency virus-1 (HIV-1) antagonizes BST2 through viral protein u (Vpu), which downregulates BST2 from the cell surface. We report the crystal structure of a protein complex containing Vpu and BST2 cytoplasmic domains and the core of the clathrin adaptor protein complex 1 (AP1). This, together with our biochemical and functional validations, reveals how Vpu hijacks the AP1-dependent membrane trafficking pathways to mistraffick BST2. Vpu mimics a canonical acidic dileucine-sorting motif to bind AP1 in the cytosol, while simultaneously interacting with BST2 in the membrane. These interactions enable Vpu to build on an intrinsic interaction between BST2 and AP1, presumably causing the observed retention of BST2 in juxtanuclear endosomes and stimulating its degradation in lysosomes. The ability of Vpu to hijack AP-dependent trafficking pathways suggests a potential common theme for Vpu-mediated downregulation of host proteins.DOI: http://dx.doi.org/10.7554/eLife.02362.001.

PubMed: 24843023
DOI: 10.7554/eLife.02362

Experimental method

X-RAY DIFFRACTION (3 Å)