Description
Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:3.3
Classification:SIGNALING PROTEIN
Release Date:2015-07-29
Deposition Date:2015-05-19
Revision Date:2015-08-05#2015-08-12#2018-02-14
Molecular Weight:403444.41
Macromolecule Type:Protein
Residue Count:3624
Atom Site Count:24665
DOI:10.2210/pdb4zwj/pdb
Abstract:
G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.
Resolution:3.3
Classification:SIGNALING PROTEIN
Release Date:2015-07-29
Deposition Date:2015-05-19
Revision Date:2015-08-05#2015-08-12#2018-02-14
Molecular Weight:403444.41
Macromolecule Type:Protein
Residue Count:3624
Atom Site Count:24665
DOI:10.2210/pdb4zwj/pdb
Abstract:
G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology.
| Date made available | 2015 |
|---|---|
| Publisher | RCSB-PDB |