6bwv

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Crystal Structure of the 4-1BB/4-1BBL ComplexCrystal Structure of the 4-1BB/4-1BBL Complex

Structural highlights

6bwv is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TNFL9_HUMAN Cytokine that binds to TNFRSF9. Induces the proliferation of activated peripheral blood T-cells. May have a role in activation-induced cell death (AICD). May play a role in cognate interactions between T-cells and B-cells/macrophages.

Publication Abstract from PubMed

4-1BBL is a member of the TNF superfamily and is the ligand for the TNFRsuperfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells and agonists of this receptor have garnered strong attention as potentialimmunotherapy agents. Broadly speaking, the structural features of TNF superfamilymembers, their receptors and ligand/receptor complexes are similar. However, apublished crystal structure of human 4-1BBL suggests that it may be unique in thisregard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members. This unusual structure also suggests that the human 4-1BB/4-1BBL complex may be structurally unique within the TNF/TNFR superfamily, but to date no structural data have been reported. Here we report the crystal structure of the human 4-1BB/4-1BBL complex at 2.4 A resolution. In this structure, 4-1BBL does not adopt the unusual trimer assembly previously reported, but instead forms a canonical bell-shaped trimer typical of other TNF superfamily members. The structure of 4-1BB is also largely canonical as is the 4-1BB/4-1BBL complex. Mutational data support the 4-1BBL structure reported here as being biologically relevant, suggesting that the previously reported structure is not. Together, the data presented here offer insight into structure/function relationships in the 4-1BB/4-1BBL system and improve our structural understanding of the TNF/TNFR superfamily more broadly.

Crystal structure of the human 4-1BB/4-1BBL complex.,Gilbreth RN, Oganesyan VY, Amdouni H, Novarra S, Grinberg L, Barnes A, Baca M J Biol Chem. 2018 May 2. pii: RA118.002803. doi: 10.1074/jbc.RA118.002803. PMID:29720399[1]

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

See Also

References

  1. Gilbreth RN, Oganesyan VY, Amdouni H, Novarra S, Grinberg L, Barnes A, Baca M. Crystal structure of the human 4-1BB/4-1BBL complex. J Biol Chem. 2018 May 2. pii: RA118.002803. doi: 10.1074/jbc.RA118.002803. PMID:29720399 doi:http://dx.doi.org/10.1074/jbc.RA118.002803

6bwv, resolution 2.40Å

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OCA