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

Citation:
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.
PDB ID: 4P6ZDownload
MMDB ID: 120133
PDB Deposition Date: 2014/3/25
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Human immunodeficiency virus type 1 (SF162 ISOLATE)
Similar Structures:
Biological Unit for 4P6Z: hexameric; determined by author and by software (PISA)
Molecular Components in 4P6Z
Label Count Molecule
Proteins (6 molecules)
1
Ap-1 Complex Subunit Gamma-1(Gene symbol: Ap1g1)
Molecule annotation
1
Ap-1 Complex Subunit Sigma-1a(Gene symbol: AP1S1)
Molecule annotation
1
Ap-1 Complex Subunit Mu-1(Gene symbol: Ap1m1)
Molecule annotation
1
Ap-1 Complex Subunit Beta-1(Gene symbol: AP1B1)
Molecule annotation
1
Protein VPU
Molecule annotation
1
Bone Marrow Stromal Antigen 2(Gene symbol: BST2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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