6DO1

Structure of nanobody-stabilized angiotensin II type 1 receptor bound to S1I8

6DO1 の概要

• エントリーDOI: 10.2210/pdb6do1/pdb
• 分子名称: Type-1 angiotensin II receptor,Soluble cytochrome b562 BRIL fusion protein, Nanobody Nb.AT110i1, Angiotensin-like peptide S1I8, ... (7 entities in total)
• 機能のキーワード: nanobody, gpcr, synthetic antibody, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 156220.47

構造登録者

Wingler, L.M.,McMahon, C.,Staus, D.P.,Lefkowitz, R.J.,Kruse, A.C. (登録日: 2018-06-08, 公開日: 2019-01-30, 最終更新日: 2024-11-06)

主引用文献

Wingler, L.M.,McMahon, C.,Staus, D.P.,Lefkowitz, R.J.,Kruse, A.C.
Distinctive Activation Mechanism for Angiotensin Receptor Revealed by a Synthetic Nanobody.
Cell, 176:479-490.e12, 2019

PubMed Abstract: The angiotensin II (AngII) type 1 receptor (AT1R) is a critical regulator of cardiovascular and renal function and is an important model for studies of G-protein-coupled receptor (GPCR) signaling. By stabilizing the receptor with a single-domain antibody fragment ("nanobody") discovered using a synthetic yeast-displayed library, we determined the crystal structure of active-state human AT1R bound to an AngII analog with partial agonist activity. The nanobody binds to the receptor's intracellular transducer pocket, stabilizing the large conformational changes characteristic of activated GPCRs. The peptide engages the AT1R through an extensive interface spanning from the receptor core to its extracellular face and N terminus, remodeling the ligand-binding cavity. Remarkably, the mechanism used to propagate conformational changes through the receptor diverges from other GPCRs at several key sites, highlighting the diversity of allosteric mechanisms among GPCRs. Our structure provides insight into how AngII and its analogs stimulate full or biased signaling, respectively.

PubMed: 30639100
DOI: 10.1016/j.cell.2018.12.006

実験手法

X-RAY DIFFRACTION (2.901 Å)