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Title: Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef

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 {mu}1 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-{mu}1 interface, which encompasses the cargo-recognition site of {mu}1 and the proline-rich strand of Nef. The Nef C terminus induces a previously unobserved conformational change in {mu}1, whereas the N terminus binds the Nef core to position it optimally for complex formation. Positively charged patches on {mu}1 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.

Authors:
; ; ; ; ;  [1];  [2];  [2]
  1. (Yale)
  2. (
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
OTHERNIH
OSTI Identifier:
1046851
Resource Type:
Journal Article
Journal Name:
Nat. Struct. Mol. Biol.
Additional Journal Information:
Journal Volume: 19; Journal Issue: (7) ; 07, 2012
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ANTIGENS; CONFORMATIONAL CHANGES; CRYSTAL STRUCTURE; HISTOCOMPATIBILITY COMPLEX; IMMUNITY; MEMBRANES; PROTEINS; SORTING; SPECIFICITY

Citation Formats

Jia, Xiaofei, Singh, Rajendra, Homann, Stefanie, Yang, Haitao, Guatelli, John, Xiong, Yong, VA), and UCSD). Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef. United States: N. p., 2012. Web. doi:10.1038/nsmb.2328.
Jia, Xiaofei, Singh, Rajendra, Homann, Stefanie, Yang, Haitao, Guatelli, John, Xiong, Yong, VA), & UCSD). Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef. United States. doi:10.1038/nsmb.2328.
Jia, Xiaofei, Singh, Rajendra, Homann, Stefanie, Yang, Haitao, Guatelli, John, Xiong, Yong, VA), and UCSD). Wed . "Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef". United States. doi:10.1038/nsmb.2328.
@article{osti_1046851,
title = {Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef},
author = {Jia, Xiaofei and Singh, Rajendra and Homann, Stefanie and Yang, Haitao and Guatelli, John and Xiong, Yong and VA) and UCSD)},
abstractNote = {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 {mu}1 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-{mu}1 interface, which encompasses the cargo-recognition site of {mu}1 and the proline-rich strand of Nef. The Nef C terminus induces a previously unobserved conformational change in {mu}1, whereas the N terminus binds the Nef core to position it optimally for complex formation. Positively charged patches on {mu}1 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.},
doi = {10.1038/nsmb.2328},
journal = {Nat. Struct. Mol. Biol.},
number = (7) ; 07, 2012,
volume = 19,
place = {United States},
year = {2012},
month = {10}
}