+検索条件
-Structure paper
タイトル | Molecular insights into atypical modes of β-arrestin interaction with seven transmembrane receptors. |
---|---|
ジャーナル・号・ページ | Science, Vol. 383, Issue 6678, Page 101-108, Year 2024 |
掲載日 | 2024年1月5日 |
著者 | Jagannath Maharana / Fumiya K Sano / Parishmita Sarma / Manish K Yadav / Longhan Duan / Tomasz M Stepniewski / Madhu Chaturvedi / Ashutosh Ranjan / Vinay Singh / Sayantan Saha / Gargi Mahajan / Mohamed Chami / Wataru Shihoya / Jana Selent / Ka Young Chung / Ramanuj Banerjee / Osamu Nureki / Arun K Shukla / |
PubMed 要旨 | β-arrestins (βarrs) are multifunctional proteins involved in signaling and regulation of seven transmembrane receptors (7TMRs), and their interaction is driven primarily by agonist-induced receptor ...β-arrestins (βarrs) are multifunctional proteins involved in signaling and regulation of seven transmembrane receptors (7TMRs), and their interaction is driven primarily by agonist-induced receptor activation and phosphorylation. Here, we present seven cryo-electron microscopy structures of βarrs either in the basal state, activated by the muscarinic receptor subtype 2 (M2R) through its third intracellular loop, or activated by the βarr-biased decoy D6 receptor (D6R). Combined with biochemical, cellular, and biophysical experiments, these structural snapshots allow the visualization of atypical engagement of βarrs with 7TMRs and also reveal a structural transition in the carboxyl terminus of βarr2 from a β strand to an α helix upon activation by D6R. Our study provides previously unanticipated molecular insights into the structural and functional diversity encoded in 7TMR-βarr complexes with direct implications for exploring novel therapeutic avenues. |
リンク | Science / PubMed:38175886 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 6.53 Å |
構造データ | EMDB-34174, PDB-8go9: EMDB-36078, PDB-8j8r: EMDB-36081, PDB-8j8v: EMDB-36082, PDB-8j8z: EMDB-36090, PDB-8j97: EMDB-36091: Muscarinic receptor (M2R) in complex with beta-arrestin1 (Low resolution full map, Cross-linked) EMDB-36093: Muscarinic receptor (M2R) in complex with beta-arrestin1 (Low resolution full map, non-crosslinked) EMDB-36110, PDB-8j9k: EMDB-36124, PDB-8ja3: EMDB-36126, PDB-8jaf: |
由来 |
|
キーワード | SIGNALING PROTEIN/IMMUNE SYSTEM / GPCR / Arrestin / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex / SYGNALING PROTEIN/IMMUNE SYSTEM / SYGNALING PROTEIN-IMMUNE SYSTEM complex |