Structural basis of mouse cytomegalovirus m152/gp40 interaction with RAE1? reveals a paradigm for MHC/MHC interaction in immune evasion.

ABSTRACT: Natural killer (NK) cells are activated by engagement of the NKG2D receptor with ligands on target cells stressed by infection or tumorigenesis. Several human and rodent cytomegalovirus (CMV) immunoevasins down-regulate surface expression of NKG2D ligands. The mouse CMV MHC class I (MHC-I)-like m152/gp40 glycoprotein down-regulates retinoic acid early inducible-1 (RAE1) NKG2D ligands as well as host MHC-I. Here we describe the crystal structure of an m152/RAE1? complex and confirm the intermolecular contacts by mutagenesis. m152 interacts in a pincer-like manner with two sites on the ?1 and ?2 helices of RAE1 reminiscent of the NKG2D interaction with RAE1. This structure of an MHC-I-like immunoevasin/MHC-I-like ligand complex explains the binding specificity of m152 for RAE1 and allows modeling of the interaction of m152 with classical MHC-I and of related viral immunoevasins.

SUBMITTER: Wang R 

PROVIDER: S-EPMC3529088 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature