+検索条件
-Structure paper
タイトル | Toward a Structural Understanding of Class B GPCR Peptide Binding and Activation. |
---|---|
ジャーナル・号・ページ | Mol Cell, Vol. 77, Issue 3, Page 656-668.e5, Year 2020 |
掲載日 | 2020年2月6日 |
著者 | Yi-Lynn Liang / Matthew J Belousoff / Peishen Zhao / Cassandra Koole / Madeleine M Fletcher / Tin T Truong / Villy Julita / George Christopoulos / H Eric Xu / Yan Zhang / Maryam Khoshouei / Arthur Christopoulos / Radostin Danev / Patrick M Sexton / Denise Wootten / |
PubMed 要旨 | Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, ...Class B G protein-coupled receptors (GPCRs) are important therapeutic targets for major diseases. Here, we present structures of peptide and Gs-bound pituitary adenylate cyclase-activating peptide, PAC1 receptor, and corticotropin-releasing factor (CRF), (CRF1) receptor. Together with recently solved structures, these provide coverage of the major class B GPCR subfamilies. Diverse orientations of the extracellular domain to the receptor core in different receptors are at least partially dependent on evolutionary conservation in the structure and nature of peptide interactions. Differences in peptide interactions to the receptor core also influence the interlinked TM2-TM1-TM6/ECL3/TM7 domain, and this is likely important in their diverse signaling. However, common conformational reorganization of ECL2, linked to reorganization of ICL2, modulates G protein contacts. Comparison between receptors reveals ICL2 as a key domain forming dynamic G protein interactions in a receptor- and ligand-specific manner. This work advances our understanding of class B GPCR activation and Gs coupling. |
リンク | Mol Cell / PubMed:32004469 |
手法 | EM (単粒子) |
解像度 | 2.65 - 3.01 Å |
構造データ | EMDB-0993: EMDB-20277: CRF1 Receptor Gs GPCR protein complex with CRF1 peptide. EMDB-20278, PDB-6p9y: EMDB-30003: |
化合物 | ChemComp-HOH: |
由来 |
|
キーワード | MEMBRANE PROTEIN / GPCR |