Crystal structure of TNFalpha complexed with a poxvirus MHC-related TNF binding protein

Nat Struct Mol Biol. 2009 Nov;16(11):1189-91. doi: 10.1038/nsmb.1683. Epub 2009 Oct 18.

Abstract

The poxvirus 2L protein binds tumor necrosis factor-alpha (TNFalpha) to inhibit host antiviral and immune responses. The 2.8-A 2L-TNFalpha structure reveals three symmetrically arranged 2L molecules per TNFalpha trimer. 2L resembles class I major histocompatibility complex (MHC) molecules but lacks a peptide-binding groove and beta2-microglobulin light chain. Overlap between the 2L and host TNF receptor-binding sites on TNFalpha rationalizes 2L inhibition of TNFalpha-TNF receptor interactions and prevention of TNFalpha-induced immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Models, Molecular
  • Poxviridae / metabolism*
  • Protein Binding
  • Protein Structure, Secondary
  • Tumor Necrosis Factor-alpha / chemistry*
  • Tumor Necrosis Factor-alpha / metabolism*
  • Viral Proteins / chemistry*
  • Viral Proteins / metabolism*

Substances

  • Histocompatibility Antigens Class I
  • Tumor Necrosis Factor-alpha
  • Viral Proteins

Associated data

  • PDB/3IT8