8K4P

Cryo-EM structure of an active Kaposi's Sarcoma-Associated Herpesvirus-G Protein-Coupled Receptor (KSHV-GPCR) in complex with Gi protein

8K4P の概要

• エントリーDOI: 10.2210/pdb8k4p/pdb
• EMDBエントリー: 36889
• 分子名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, G protein-coupled receptor, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (4 entities in total)
• 機能のキーワード: kaposi's sarcoma-associated herpesvirus-g protein-coupled receptor, kshv-gpcr, hhv8, viral protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 117032.59

構造登録者

Liu, Y.Z.,Liu, A.J. (登録日: 2023-07-20, 公開日: 2024-07-24, 最終更新日: 2025-07-02)

主引用文献

Liu, A.,Liu, Y.,Llinas Del Torrent Masachs, C.,Zhang, W.,Pardo, L.,Ye, R.D.
Structural insights into KSHV-GPCR constitutive activation and CXCL1 chemokine recognition.
Proc.Natl.Acad.Sci.USA, 121:e2403217121-e2403217121, 2024

PubMed Abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a viral G protein-coupled receptor, KSHV-GPCR, that contributes to KSHV immune evasion and pathogenesis of Kaposi's sarcoma. KSHV-GPCR shares a high similarity with CXC chemokine receptors CXCR2 and can be activated by selected chemokine ligands. Like other herpesvirus-encoded GPCRs, KSHV-GPCR is characterized by its constitutive activity by coupling to various G proteins. We investigated the structural basis of ligand-dependent and constitutive activation of KSHV-GPCR, obtaining high-resolution cryo-EM structures of KSHV-GPCR-Gi complexes with and without the bound CXCL1 chemokine. Analysis of the apo-KSHV-GPCR-Gi structure (2.81 Å) unraveled the involvement of extracellular loop 2 in constitutive activation of the receptor. In comparison, the CXCL1-bound KSHV-GPCR-Gi structure (3.01 Å) showed a two-site binding mode and provided detailed information of CXCL1 binding to a chemokine receptor. The dual activation mechanism employed by KSHV-GPCR represents an evolutionary adaptation for immune evasion and contributes to the pathogenesis of Kaposi's sarcoma. Together with results from functional assays that confirmed the structural models, these findings may help to develop therapeutic strategies for KSHV infection.

PubMed: 39378089
DOI: 10.1073/pnas.2403217121

実験手法

ELECTRON MICROSCOPY (2.81 Å)