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

Publication Type:

Journal Article


Nat Struct Mol Biol, Volume 19, Issue 7, p.701-6 (2012)


Adaptation, Physiological, Cell Line, Gene Products, nef, HIV-1, Humans, Immune Evasion, Models, Molecular, Protein Conformation, Static Electricity


<p>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.</p>