4EN2

HIV-1 Nef in complex with MHC-I cytoplasmic domain and Mu1 adaptin subunit of AP1 adaptor (second domain)

Summary for 4EN2

• Entry DOI: 10.2210/pdb4en2/pdb
• Related: 4EMZ
• Descriptor: AP-1 complex subunit mu-1, Protein Nef, MHC-I, ... (4 entities in total)
• Functional Keywords: human immunodeficiency virus 1, hiv, nef, mhc-i, antigen presentation, host defense, adaptor protein complex 1, mu1 adaptin subunit, sorting motif recognition, clasp, membrane trafficking, viral hijacking, viral protein-immune system complex, viral protein/immune system
• Biological source: Mus musculus (mouse); More
• Cellular location: Golgi apparatus: P35585; Host cell membrane ; Lipid-anchor ; Cytoplasmic side : Q90VU7
• Total number of polymer chains: 6
• Total formula weight: 113520.66

Authors

Jia, X.,Xiong, Y. (deposition date: 2012-04-12, release date: 2012-06-20, Last modification date: 2024-02-28)

Primary citation

Jia, X.,Singh, R.,Homann, S.,Yang, H.,Guatelli, J.,Xiong, Y.
Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef.
Nat.Struct.Mol.Biol., 19:701-706, 2012

PubMed Abstract: The HIV-1 protein Nef inhibits antigen presentation by class I major histocompatibility complex (MHC-I). We determined the mechanism of this activity by solving the crystal structure of a protein complex comprising Nef, the MHC-I cytoplasmic domain (MHC-I CD) and the μ1 subunit of the clathrin adaptor protein complex 1. A ternary, cooperative interaction clamps the MHC-I CD into a narrow binding groove at the Nef-μ1 interface, which encompasses the cargo-recognition site of μ1 and the proline-rich strand of Nef. The Nef C terminus induces a previously unobserved conformational change in μ1, whereas the N terminus binds the Nef core to position it optimally for complex formation. Positively charged patches on μ1 recognize acidic clusters in Nef and MHC-I. The structure shows how Nef functions as a clathrin-associated sorting protein to alter the specificity of host membrane trafficking and enable viral evasion of adaptive immunity.

PubMed: 22705789
DOI: 10.1038/nsmb.2328

Experimental method

X-RAY DIFFRACTION (2.58 Å)