9AST

Cryo-EM structure of XCR1 signaling complex

9AST の概要

• エントリーDOI: 10.2210/pdb9ast/pdb
• EMDBエントリー: 43825
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-1, Lymphotactin, Chemokine XC receptor 1,Non structural polyprotein, ... (6 entities in total)
• 機能のキーワード: gpcr, xcl1, membrane protein, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 189941.38

構造登録者

Zhang, X.,Zhang, C. (登録日: 2024-02-26, 公開日: 2024-12-11)

主引用文献

Zhang, X.,Schlimgen, R.R.,Singh, S.,Tomani, M.P.,Volkman, B.F.,Zhang, C.
Molecular basis for chemokine recognition and activation of XCR1.
Proc.Natl.Acad.Sci.USA, 121:e2405732121-e2405732121, 2024

PubMed Abstract: 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 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.

PubMed: 39565315
DOI: 10.1073/pnas.2405732121

実験手法

ELECTRON MICROSCOPY (3.07 Å)