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3it8

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3it8, resolution 2.80Å ()
Ligands:
Gene: TNF (Homo sapiens), 2L (Viruses)
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

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

Publication Abstract from PubMed

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.

Crystal structure of TNFalpha complexed with a poxvirus MHC-related TNF binding protein., Yang Z, West AP Jr, Bjorkman PJ, Nat Struct Mol Biol. 2009 Nov;16(11):1189-91. Epub 2009 Oct 18. PMID:019838188

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Disease

[TNFA_HUMAN] Genetic variations in TNF are a cause of susceptibility psoriatic arthritis (PSORAS) [MIM:607507]. PSORAS is an inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoidlike pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).

Function

[TNFA_HUMAN] Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation.[1] The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.[2]

About this Structure

3it8 is a 12 chain structure with sequence from Homo sapiens and Viruses. Full crystallographic information is available from OCA.

Reference

  1. Friedmann E, Hauben E, Maylandt K, Schleeger S, Vreugde S, Lichtenthaler SF, Kuhn PH, Stauffer D, Rovelli G, Martoglio B. SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production. Nat Cell Biol. 2006 Aug;8(8):843-8. Epub 2006 Jul 9. PMID:16829952 doi:10.1038/ncb1440
  2. Friedmann E, Hauben E, Maylandt K, Schleeger S, Vreugde S, Lichtenthaler SF, Kuhn PH, Stauffer D, Rovelli G, Martoglio B. SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production. Nat Cell Biol. 2006 Aug;8(8):843-8. Epub 2006 Jul 9. PMID:16829952 doi:10.1038/ncb1440

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