9ast | pdb_00009ast

Cryo-EM structure of XCR1 signaling complex

spinqualitylabelsall models 9ast, resolution 3.07Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ast is a 6 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.07Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function XCL1_HUMAN Chemotactic activity for lymphocytes but not for monocytes or neutrophils. Publication Abstract from PubMed The X-C motif chemokine receptor XCR1, which selectively binds to the chemokine XCL1, is highly expressed in conventional dendritic cells subtype 1 (cDC1s) and crucial for their activation. Modulating XCR1 signaling in cDC1s could offer novel opportunities in cancer immunotherapy and vaccine development by enhancing the antigen presentation function of cDC1s. To investigate the molecular mechanism of XCL-induced XCR1 signaling, we determined a high-resolution structure of the human XCR1 and G(i) complex with an engineered form of XCL1, XCL1 CC3, by cryoelectron microscopy. Through mutagenesis and structural analysis, we elucidated the molecular details for the binding of the N-terminal segment of XCL1 CC3, which is vital for activating XCR1. The unique arrangement within the XCL1 CC3 binding site confers specificity for XCL1 in XCR1. We propose an activation mechanism for XCR1 involving structural alterations of key residues at the bottom of the XCL1 binding pocket. These detailed insights into XCL1 CC3-XCR1 interaction and XCR1 activation pave the way for developing novel XCR1-targeted therapeutics. Molecular basis for chemokine recognition and activation of XCR1.,Zhang X, Schlimgen RR, Singh S, Tomani MP, Volkman BF, Zhang C Proc Natl Acad Sci U S A. 2024 Nov 26;121(48):e2405732121. doi: , 10.1073/pnas.2405732121. Epub 2024 Nov 20. PMID:39565315 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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