6DO1
Structure of nanobody-stabilized angiotensin II type 1 receptor bound to S1I8
Summary for 6DO1
| Entry DOI | 10.2210/pdb6do1/pdb |
| Descriptor | Type-1 angiotensin II receptor,Soluble cytochrome b562 BRIL fusion protein, Nanobody Nb.AT110i1, Angiotensin-like peptide S1I8, ... (7 entities in total) |
| Functional Keywords | nanobody, gpcr, synthetic antibody, membrane protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 8 |
| Total formula weight | 156220.47 |
| Authors | Wingler, L.M.,McMahon, C.,Staus, D.P.,Lefkowitz, R.J.,Kruse, A.C. (deposition date: 2018-06-08, release date: 2019-01-30, Last modification date: 2024-11-06) |
| Primary citation | 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 Cited by 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: 30639100DOI: 10.1016/j.cell.2018.12.006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.901 Å) |
Structure validation
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