Published November 2009 | Version Accepted Version + Supplemental Material
Journal Article Open

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

  • 1. ROR icon California Institute of Technology

Abstract

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.

Additional Information

© 2009 Nature Publishing Group, a division of Macmillan Publishers Limited. Received 29 April; accepted 26 August; published online 18 October 2009. Diffraction data were collected at the Stanford Synchrotron Radiation Laboratory. We thank the Caltech Protein Expression Center and the Gordon and Betty Moore Foundation for support of the Molecular Observatory at Caltech. This work was supported by a Life Sciences Research Foundation Fellowship (Z.Y.) and the Howard Hughes Medical Institute. Accession codes. Protein Data Bank: Coordinates and X-ray crystallographic data for the 2L–TNFalpha complex have been deposited with accession code 3IT8. Author Contributions: Z.Y. and A.P.W. performed the experiments; Z.Y., A.P.W. and P.J.B. analyzed and interpreted that data; P.J.B. oversaw the project.

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Accepted Version - nihms172308.pdf

Supplemental Material - nsmb.1683-S1.pdf

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Additional details

Identifiers

PMCID
PMC2819277
Eprint ID
16781
DOI
10.1038/nsmb.1683
Resolver ID
CaltechAUTHORS:20091123-100928279

Related works

Describes
10.1038/nsmb.1683 (DOI)

Funding

Caltech Protein Expression Center
Gordon and Betty Moore Foundation
Life Sciences Research Foundation
Howard Hughes Medical Institute (HHMI)

Dates

Created
2009-11-24
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Updated
2021-11-08
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