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-Structure paper
タイトル | Molecular Determinant Underlying Selective Coupling of Primary G-Protein by Class A GPCRs. |
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ジャーナル・号・ページ | Adv Sci (Weinh), Vol. 11, Issue 23, Page e2310120, Year 2024 |
掲載日 | 2024年4月22日 |
著者 | Qingya Shen / Xinyan Tang / Xin Wen / Shizhuo Cheng / Peng Xiao / Shao-Kun Zang / Dan-Dan Shen / Lei Jiang / Yanrong Zheng / Huibing Zhang / Haomang Xu / Chunyou Mao / Min Zhang / Weiwei Hu / Jin-Peng Sun / Yan Zhang / Zhong Chen / |
PubMed 要旨 | G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling of primary G-protein remains elusive. ...G-protein-coupled receptors (GPCRs) transmit downstream signals predominantly via G-protein pathways. However, the conformational basis of selective coupling of primary G-protein remains elusive. Histamine receptors HR and HR couple with G- or G-proteins respectively. Here, three cryo-EM structures of HR-G and HR-G complexes are presented at a global resolution of 2.6-2.7 Å. These structures reveal the unique binding pose for endogenous histamine in HR, wherein the amino group interacts with E206 of HR instead of the conserved D114 of other aminergic receptors. Furthermore, comparative analysis of the HR-G and HR-G complexes reveals that the structural geometry of TM5/TM6 determines the primary G-protein selectivity in histamine receptors. Machine learning (ML)-based structuromic profiling and functional analysis of class A GPCR-G-protein complexes illustrate that TM5 length, TM5 tilt, and TM6 outward movement are key determinants of the G and G selectivity among the whole Class A family. Collectively, the findings uncover the common structural geometry within class A GPCRs that determines the primary G- and G-coupling selectivity. |
リンク | Adv Sci (Weinh) / PubMed:38647423 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.7 - 3.0 Å |
構造データ | EMDB-39582, PDB-8yut: EMDB-39583, PDB-8yuu: EMDB-39584, PDB-8yuv: |
化合物 | PDB-1d67: ChemComp-CLR: ChemComp-HSM: PDB-1ly4: |
由来 |
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キーワード | MEMBRANE PROTEIN/IMMUNE SYSTEM / GPCR / H2R / Histamine Receptor / MEMBRANE PROTEIN-IMMUNE SYSTEM complex / H3R |