4zwj
From Proteopedia
Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser
Structural highlights
DiseaseOPSD_HUMAN Congenital stationary night blindness;Retinitis punctata albescens;Retinitis pigmentosa. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. FunctionOPSD_HUMAN Photoreceptor required for image-forming vision at low light intensity (PubMed:7846071, PubMed:8107847). Required for photoreceptor cell viability after birth (PubMed:12566452, PubMed:2215617). Light-induced isomerization of the chromophore 11-cis-retinal to all-trans-retinal triggers a conformational change that activates signaling via G-proteins (PubMed:26200343, PubMed:28524165, PubMed:28753425, PubMed:8107847). Subsequent receptor phosphorylation mediates displacement of the bound G-protein alpha subunit by the arrestin SAG and terminates signaling (PubMed:26200343, PubMed:28524165).[1] [2] [3] [4] [5] [6] [7] ENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[8] ARRS_MOUSE Binds to photoactivated, phosphorylated RHO and terminates RHO signaling via G-proteins by competing with G-proteins for the same binding site on RHO (PubMed:16421323, PubMed:9333241). May play a role in preventing light-dependent degeneration of retinal photoreceptor cells (PubMed:16421323).[9] [10] Publication Abstract from PubMedG-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 approximately 20 degrees 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. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.,Kang Y, Zhou XE, Gao X, He Y, Liu W, Ishchenko A, Barty A, White TA, Yefanov O, Han GW, Xu Q, de Waal PW, Ke J, Tan MH, Zhang C, Moeller A, West GM, Pascal BD, Van Eps N, Caro LN, Vishnivetskiy SA, Lee RJ, Suino-Powell KM, Gu X, Pal K, Ma J, Zhi X, Boutet S, Williams GJ, Messerschmidt M, Gati C, Zatsepin NA, Wang D, James D, Basu S, Roy-Chowdhury S, Conrad CE, Coe J, Liu H, Lisova S, Kupitz C, Grotjohann I, Fromme R, Jiang Y, Tan M, Yang H, Li J, Wang M, Zheng Z, Li D, Howe N, Zhao Y, Standfuss J, Diederichs K, Dong Y, Potter CS, Carragher B, Caffrey M, Jiang H, Chapman HN, Spence JC, Fromme P, Weierstall U, Ernst OP, Katritch V, Gurevich VV, Griffin PR, Hubbell WL, Stevens RC, Cherezov V, Melcher K, Xu HE Nature. 2015 Jul 30;523(7562):561-7. doi: 10.1038/nature14656. Epub 2015 Jul 22. PMID:26200343[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Escherichia virus T4 | Homo sapiens | Large Structures | Mus musculus | Barty A | Basu S | Boutet S | Caffrey M | Caro LN | Carragher B | Chapman HN | Cherezov V | Coe J | Conrad C | Diederichs K | Dong Y | Eps NV | Ernst OP | Fromme P | Fromme R | Gao X | Gati C | Griffin PR | Grotjohann I | Gu X | Gurevich VV | Han GW | He Y | Howe N | Hubbell WL | Ishchenko A | James D | Jiang H | Jiang Y | Kang Y | Katritch V | Ke J | Kupitz C | Lee RJ | Li D | Li J | Lisova S | Liu H | Liu W | Ma J | Melcher K | Messerschmidt M | Moeller A | Pal K | Pascal B | Potter CS | Roy-Chowdhury S | Spence JCH | Standfuss J | Stevens RC | Suino-Powell KM | Tan M | Tan MHE | Vishnivetskiy SA | Wang D | Wang M | Weierstall U | West GM | White TA | Williams GJ | Xu HE | Xu Q | Yang H | Yefanov O | Zatsepin NA | Zhang C | Zhao Y | Zheng Z | Zhi X | Zhou XE | De Waal PW