4zwj

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

Structural highlights

4zwj is a 4 chain structure with sequence from Escherichia virus T4, Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.302Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

OPSD_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.

Function

OPSD_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 PubMed

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 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.

References

↑ Noorwez SM, Kuksa V, Imanishi Y, Zhu L, Filipek S, Palczewski K, Kaushal S. Pharmacological chaperone-mediated in vivo folding and stabilization of the P23H-opsin mutant associated with autosomal dominant retinitis pigmentosa. J Biol Chem. 2003 Apr 18;278(16):14442-14450. PMID:12566452 doi:10.1074/jbc.M300087200
↑ Dryja TP, McGee TL, Hahn LB, Cowley GS, Olsson JE, Reichel E, Sandberg MA, Berson EL. Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. N Engl J Med. 1990 Nov 8;323(19):1302-7. PMID:2215617 doi:10.1056/NEJM199011083231903
↑ 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. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature. 2015 Jul 30;523(7562):561-7. doi: 10.1038/nature14656. Epub 2015 Jul 22. PMID:26200343 doi:https://dx.doi.org/10.1038/nature14656
↑ Zhou XE, He Y, de Waal PW, Gao X, Kang Y, Van Eps N, Yin Y, Pal K, Goswami D, White TA, Barty A, Latorraca NR, Chapman HN, Hubbell WL, Dror RO, Stevens RC, Cherezov V, Gurevich VV, Griffin PR, Ernst OP, Melcher K, Xu HE. Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors. Cell. 2017 Jul 27;170(3):457-469.e13. doi: 10.1016/j.cell.2017.07.002. PMID:28753425 doi:https://dx.doi.org/10.1016/j.cell.2017.07.002
↑ Sieving PA, Richards JE, Naarendorp F, Bingham EL, Scott K, Alpern M. Dark-light: model for nightblindness from the human rhodopsin Gly-90-->Asp mutation. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):880-4. PMID:7846071 doi:10.1073/pnas.92.3.880
↑ Rao VR, Cohen GB, Oprian DD. Rhodopsin mutation G90D and a molecular mechanism for congenital night blindness. Nature. 1994 Feb 17;367(6464):639-42. PMID:8107847 doi:10.1038/367639a0
↑ He Y, Gao X, Goswami D, Hou L, Pal K, Yin Y, Zhao G, Ernst OP, Griffin P, Melcher K, Xu HE. Molecular assembly of rhodopsin with G protein-coupled receptor kinases. Cell Res. 2017 Jun;27(6):728-747. PMID:28524165 doi:10.1038/cr.2017.72
↑ Moussa SH, Kuznetsov V, Tran TA, Sacchettini JC, Young R. Protein determinants of phage T4 lysis inhibition. Protein Sci. 2012 Apr;21(4):571-82. doi: 10.1002/pro.2042. Epub 2012 Mar 2. PMID:22389108 doi:https://dx.doi.org/10.1002/pro.2042
↑ Burns ME, Mendez A, Chen CK, Almuete A, Quillinan N, Simon MI, Baylor DA, Chen J. Deactivation of phosphorylated and nonphosphorylated rhodopsin by arrestin splice variants. J Neurosci. 2006 Jan 18;26(3):1036-44. PMID:16421323 doi:10.1523/JNEUROSCI.3301-05.2006
↑ Xu J, Dodd RL, Makino CL, Simon MI, Baylor DA, Chen J. Prolonged photoresponses in transgenic mouse rods lacking arrestin. Nature. 1997 Oct 2;389(6650):505-9. PMID:9333241 doi:10.1038/39068
↑ 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. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature. 2015 Jul 30;523(7562):561-7. doi: 10.1038/nature14656. Epub 2015 Jul 22. PMID:26200343 doi:https://dx.doi.org/10.1038/nature14656

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OCA

[1] Noorwez SM, Kuksa V, Imanishi Y, Zhu L, Filipek S, Palczewski K, Kaushal S. Pharmacological chaperone-mediated in vivo folding and stabilization of the P23H-opsin mutant associated with autosomal dominant retinitis pigmentosa. J Biol Chem. 2003 Apr 18;278(16):14442-14450. PMID:12566452 doi:10.1074/jbc.M300087200

[2] Dryja TP, McGee TL, Hahn LB, Cowley GS, Olsson JE, Reichel E, Sandberg MA, Berson EL. Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. N Engl J Med. 1990 Nov 8;323(19):1302-7. PMID:2215617 doi:10.1056/NEJM199011083231903

[3] 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. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature. 2015 Jul 30;523(7562):561-7. doi: 10.1038/nature14656. Epub 2015 Jul 22. PMID:26200343 doi:https://dx.doi.org/10.1038/nature14656

[4] Zhou XE, He Y, de Waal PW, Gao X, Kang Y, Van Eps N, Yin Y, Pal K, Goswami D, White TA, Barty A, Latorraca NR, Chapman HN, Hubbell WL, Dror RO, Stevens RC, Cherezov V, Gurevich VV, Griffin PR, Ernst OP, Melcher K, Xu HE. Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors. Cell. 2017 Jul 27;170(3):457-469.e13. doi: 10.1016/j.cell.2017.07.002. PMID:28753425 doi:https://dx.doi.org/10.1016/j.cell.2017.07.002

[5] Sieving PA, Richards JE, Naarendorp F, Bingham EL, Scott K, Alpern M. Dark-light: model for nightblindness from the human rhodopsin Gly-90-->Asp mutation. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):880-4. PMID:7846071 doi:10.1073/pnas.92.3.880

[6] Rao VR, Cohen GB, Oprian DD. Rhodopsin mutation G90D and a molecular mechanism for congenital night blindness. Nature. 1994 Feb 17;367(6464):639-42. PMID:8107847 doi:10.1038/367639a0

[7] He Y, Gao X, Goswami D, Hou L, Pal K, Yin Y, Zhao G, Ernst OP, Griffin P, Melcher K, Xu HE. Molecular assembly of rhodopsin with G protein-coupled receptor kinases. Cell Res. 2017 Jun;27(6):728-747. PMID:28524165 doi:10.1038/cr.2017.72

[8] Moussa SH, Kuznetsov V, Tran TA, Sacchettini JC, Young R. Protein determinants of phage T4 lysis inhibition. Protein Sci. 2012 Apr;21(4):571-82. doi: 10.1002/pro.2042. Epub 2012 Mar 2. PMID:22389108 doi:https://dx.doi.org/10.1002/pro.2042

[9] Burns ME, Mendez A, Chen CK, Almuete A, Quillinan N, Simon MI, Baylor DA, Chen J. Deactivation of phosphorylated and nonphosphorylated rhodopsin by arrestin splice variants. J Neurosci. 2006 Jan 18;26(3):1036-44. PMID:16421323 doi:10.1523/JNEUROSCI.3301-05.2006

[10] Xu J, Dodd RL, Makino CL, Simon MI, Baylor DA, Chen J. Prolonged photoresponses in transgenic mouse rods lacking arrestin. Nature. 1997 Oct 2;389(6650):505-9. PMID:9333241 doi:10.1038/39068

[11] 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. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature. 2015 Jul 30;523(7562):561-7. doi: 10.1038/nature14656. Epub 2015 Jul 22. PMID:26200343 doi:https://dx.doi.org/10.1038/nature14656

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4zwj

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

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

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