Unusual mode of dimerization of retinitis pigmentosa-associated F220C rhodopsin.
Unusual mode of dimerization of retinitis pigmentosa-associated F220C rhodopsin.
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DOI：
10.1038/s41598-021-90039-3
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发表时间：
2021-05-18
影响因子：
4.6
通讯作者：
Menon AK
中科院分区：
文献类型：
--
作者：
Khelashvili G;Pillai AN;Lee J;Pandey K;Payne AM;Siegel Z;Cuendet MA;Lewis TR;Arshavsky VY;Broichhagen J;Levitz J;Menon AK
Mutations in the G protein-coupled receptor (GPCR) rhodopsin are a common cause of autosomal dominant retinitis pigmentosa, a blinding disease. Rhodopsin self-associates in the membrane, and the purified monomeric apo-protein opsin dimerizes in vitro as it transitions from detergent micelles to reconstitute into a lipid bilayer. We previously reported that the retinitis pigmentosa-linked F220C opsin mutant fails to dimerize in vitro, reconstituting as a monomer. Using fluorescence-based assays and molecular dynamics simulations we now report that whereas wild-type and F220C opsin display distinct dimerization propensities in vitro as previously shown, they both dimerize in the plasma membrane of HEK293 cells. Unexpectedly, molecular dynamics simulations show that F220C opsin forms an energetically favored dimer in the membrane when compared with the wild-type protein. The conformation of the F220C dimer is unique, with transmembrane helices 5 and 6 splayed apart, promoting widening of the intracellular vestibule of each protomer and influx of water into the protein interior. FRET experiments with SNAP-tagged wild-type and F220C opsin expressed in HEK293 cells are consistent with this conformational difference. We speculate that the unusual mode of dimerization of F220C opsin in the membrane may have physiological consequences.
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影响因子：
4.6
作者：
Lan TH;Liu Q;Li C;Wu G;Steyaert J;Lambert NA
通讯作者：
Lambert NA
影响因子：
7.7
作者：
Gutzeit, Vanessa A.;Thibado, Jordana;Levitz, Joshua
通讯作者：
Levitz, Joshua
影响因子：
64.8
作者：
Fotiadis, D;Liang, Y;Palczewski, K
通讯作者：
Palczewski, K
影响因子：
3
作者：
Lee, MS;Feig, M;Brooks, CL
通讯作者：
Brooks, CL
影响因子：
5.5
作者：
Best, Robert B.;Zhu, Xiao;Shim, Jihyun;Lopes, Pedro E. M.;Mittal, Jeetain;Feig, Michael;MacKerell, Alexander D., Jr.
通讯作者：
MacKerell, Alexander D., Jr.