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The first GPCR/arrestin complex structure released

已有 2993 次阅读 2015-7-23 14:54 |个人分类:科研笔记|系统分类:科研笔记

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser

Nature (2015) doi:10.1038/nature14656

full text
PDB: 4ZWJ
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.

Although there is a RHO/arrestin-peptide complex structure was released in Nature Communication (PDB: 4PXF), the electron density doesn't fit the model at all and many ambigious details were observed in this artificial model. The latest RHO/arrestin structure released today, was the first GPCR/arrestin complex structure that arrestin was present in full length. Superimposing  RHO/arrestin-peptide (PDB: 4PXF) and the full length one (PDB: 4ZWJ) indicated huge differences.


The structure of the rhodopsin–arrestin complex (PDB: 4ZWJ)






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