Crystal structure of TNFα complexed with a poxvirus MHC-related TNF binding protein
- 18 October 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Structural & Molecular Biology
- Vol. 16 (11), 1189-1191
- https://doi.org/10.1038/nsmb.1683
Abstract
The poxvirus 2L protein binds tumor necrosis factor-α (TNFα). Structural data now indicate that 2L interacts with TNFα at a site overlapping with that for its receptor, arguing for the basis of inhibition of receptor interaction and TNFα-induced immune responses. The poxvirus 2L protein binds tumor necrosis factor-α (TNFα) to inhibit host antiviral and immune responses. The 2.8-Å 2L–TNFα structure reveals three symmetrically arranged 2L molecules per TNFα trimer. 2L resembles class I major histocompatibility complex (MHC) molecules but lacks a peptide-binding groove and β2-microglobulin light chain. Overlap between the 2L and host TNF receptor-binding sites on TNFα rationalizes 2L inhibition of TNFα–TNF receptor interactions and prevention of TNFα-induced immune responses.Keywords
This publication has 18 references indexed in Scilit:
- Structure–Function Relationship of Tumor Necrosis Factor (TNF) and Its Receptor Interaction Based on 3D Structural Analysis of a Fully Active TNFR1-Selective TNF MutantJournal of Molecular Biology, 2009
- Structure of UL18, a peptide-binding viral MHC mimic, bound to a host inhibitory receptorProceedings of the National Academy of Sciences of the United States of America, 2008
- Structure of CrmE, a Virus-encoded Tumour Necrosis Factor ReceptorJournal of Molecular Biology, 2007
- Biologic therapies in rheumatology: lessons learned, future directionsNature Reviews Drug Discovery, 2007
- Modulation of Tumor Necrosis Factor by Microbial PathogensPLoS Pathogens, 2006
- Structure of a Pheromone Receptor-Associated MHC Molecule with an Open and Empty GroovePLoS Biology, 2005
- Minimizing the immunogenicity of protein therapeuticsDrug Discovery Today, 2004
- Inactivation of TNF Signaling by Rationally Designed Dominant-Negative TNF VariantsScience, 2003
- Crystal Structure of the MHC Class I Homolog MIC-A, a γδ T Cell LigandImmunity, 1999
- Shape Complementarity at Protein/Protein InterfacesJournal of Molecular Biology, 1993