| Structural highlights
7kx0 is a 6 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 2.69Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
CD70_HUMAN Combined immunodeficiency due to CD70 deficiency. The disease is caused by variants affecting the gene represented in this entry.
Function
CD70_HUMAN Expressed at the plasma membrane of B cells, it is the ligand of the CD27 receptor which is specifically expressed at the surface of T cells (PubMed:28011863, PubMed:28011864, PubMed:8387892). The CD70-CD27 signaling pathway mediates antigen-specific T cell activation and expansion which in turn provides immune surveillance of B cells (PubMed:28011863, PubMed:28011864).[1] [2] [3]
Publication Abstract from PubMed
CD27 is a tumor necrosis factor (TNF) receptor, which stimulates lymphocytes and promotes their differentiation upon activation by TNF ligand CD70. Activation of the CD27 receptor provides a costimulatory signal to promote T cell, B cell, and NK cell activity to facilitate antitumor and anti-infection immunity. Aberrant increased and focused expression of CD70 on many tumor cells renders CD70 an attractive therapeutic target for direct tumor killing. However, despite their use as drug targets to treat cancers, the molecular basis and atomic details of CD27 and CD70 interaction remain elusive. Here we report the crystal structure of human CD27 in complex with human CD70. Analysis of our structure shows that CD70 adopts a classical TNF ligand homotrimeric assembly to engage CD27 receptors in a 3:3 stoichiometry. By combining structural and rational mutagenesis data with reported disease-correlated mutations, we identified the key amino acid residues of CD27 and CD70 that control this interaction. We also report increased potency for plate-bound CD70 constructs compared with solution-phase ligand in a functional activity to stimulate T-cells in vitro. These findings offer new mechanistic insight into this critical costimulatory interaction.
Structural delineation and phase-dependent activation of the costimulatory CD27:CD70 complex.,Liu W, Maben Z, Wang C, Lindquist KC, Li M, Rayannavar V, Lopez Armenta I, Nager A, Pascua E, Dominik PK, Oyen D, Wang H, Roach RC, Allan CM, Mosyak L, Chaparro-Riggers J J Biol Chem. 2021 Oct;297(4):101102. doi: 10.1016/j.jbc.2021.101102. Epub 2021 , Aug 20. PMID:34419446[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Izawa K, Martin E, Soudais C, Bruneau J, Boutboul D, Rodriguez R, Lenoir C, Hislop AD, Besson C, Touzot F, Picard C, Callebaut I, de Villartay JP, Moshous D, Fischer A, Latour S. Inherited CD70 deficiency in humans reveals a critical role for the CD70-CD27 pathway in immunity to Epstein-Barr virus infection. J Exp Med. 2017 Jan;214(1):73-89. PMID:28011863 doi:10.1084/jem.20160784
- ↑ Abolhassani H, Edwards ES, Ikinciogullari A, Jing H, Borte S, Buggert M, Du L, Matsuda-Lennikov M, Romano R, Caridha R, Bade S, Zhang Y, Frederiksen J, Fang M, Bal SK, Haskologlu S, Dogu F, Tacyildiz N, Matthews HF, McElwee JJ, Gostick E, Price DA, Palendira U, Aghamohammadi A, Boisson B, Rezaei N, Karlsson AC, Lenardo MJ, Casanova JL, Hammarström L, Tangye SG, Su HC, Pan-Hammarström Q. Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency. J Exp Med. 2017 Jan;214(1):91-106. PMID:28011864 doi:10.1084/jem.20160849
- ↑ Goodwin RG, Alderson MR, Smith CA, Armitage RJ, VandenBos T, Jerzy R, Tough TW, Schoenborn MA, Davis-Smith T, Hennen K, et al.. Molecular and biological characterization of a ligand for CD27 defines a new family of cytokines with homology to tumor necrosis factor. Cell. 1993 May 7;73(3):447-56. PMID:8387892 doi:10.1016/0092-8674(93)90133-b
- ↑ Liu W, Maben Z, Wang C, Lindquist KC, Li M, Rayannavar V, Lopez Armenta I, Nager A, Pascua E, Dominik PK, Oyen D, Wang H, Roach RC, Allan CM, Mosyak L, Chaparro-Riggers J. Structural delineation and phase-dependent activation of the costimulatory CD27:CD70 complex. J Biol Chem. 2021 Oct;297(4):101102. PMID:34419446 doi:10.1016/j.jbc.2021.101102
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