Structural basis of evasion of cellular adaptive immunity by HIV-1 Nef.
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.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
Xiaofei
X
Jia
Rajendra
R
Singh
Stefanie
S
Homann
Haitao
H
Yang
John
J
Guatelli
Yong
Y
Xiong
D000222:Adaptation, Physiological / Q000276:immunology*; D002460:Cell Line; D015693:Gene Products, nef / Q000737:chemistry*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D057131:Immune Evasion; D008958:Models, Molecular; D011487:Protein Conformation; D055672:Static Electricity
D015693:Gene Products, nef