National Center for
4EMZ: Hiv-1 Nef In Complex With Mhc-I Cytoplasmic Domain And Mu1 Adaptin Subunit Of Ap1 Adaptor (Second Domain)
Nat. Struct. Mol. Biol. (2012) 19 p.701-706
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 mu1 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-mu1 interface, which encompasses the cargo-recognition site of mu1 and the proline-rich strand of Nef. The Nef C terminus induces a previously unobserved conformational change in mu1, whereas the N terminus binds the Nef core to position it optimally for complex formation. Positively charged patches on mu1 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.