A putative structural mechanism underlying the antithetic effect of homologous rnd1 and rhod gtpases in mammalian plexin regulation
Yanyan Liu, Pu Ke, Yi Chun Kuo, Yuxiao Wang, Xuewu Zhang, Chen Song, Yibing Shan
Pharmacology - Zhang Lab
Plexins are semaphorin receptors that play essential roles in mammalian neuronal axon guidance and in many other important mammalian biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism and is modulated by small GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations, we showed that RND1 reinforces the plexin dimerization interface, whereas RhoD destabilizes it due to their differential interaction with the cell membrane. Upon binding plexin at the Rho-GTPase-binding domain (RBD), RND1 and RhoD interact differently with the inner leaflet of the cell membrane and exert opposite effects on the dimerization interface via an allosteric network involving the RBD, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively charged membrane interface.
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plexin Medicine & Life Sciences 100%
GTP Phosphohydrolases Medicine & Life Sciences 72%
Dimerization Chemical Compounds 58%
rho GTP-Binding Proteins Medicine & Life Sciences 48%
Semaphorins Medicine & Life Sciences 36%
Axon Guidance Medicine & Life Sciences 32%
Cell Membrane Medicine & Life Sciences 18%
Liu, Y., Ke, P., Kuo, Y. C., Wang, Y., Zhang, X., Song, C., & Shan, Y. (2021). A putative structural mechanism underlying the antithetic effect of homologous rnd1 and rhod gtpases in mammalian plexin regulation. eLife, 10, [e64304]. https://doi.org/10.7554/eLife.64304
A putative structural mechanism underlying the antithetic effect of homologous rnd1 and rhod gtpases in mammalian plexin regulation. / Liu, Yanyan; Ke, Pu; Kuo, Yi Chun; Wang, Yuxiao; Zhang, Xuewu; Song, Chen; Shan, Yibing.
In: eLife, Vol. 10, e64304, 06.2021.
Liu, Y, Ke, P, Kuo, YC, Wang, Y, Zhang, X, Song, C & Shan, Y 2021, 'A putative structural mechanism underlying the antithetic effect of homologous rnd1 and rhod gtpases in mammalian plexin regulation', eLife, vol. 10, e64304. https://doi.org/10.7554/eLife.64304
Liu Y, Ke P, Kuo YC, Wang Y, Zhang X, Song C et al. A putative structural mechanism underlying the antithetic effect of homologous rnd1 and rhod gtpases in mammalian plexin regulation. eLife. 2021 Jun;10. e64304. https://doi.org/10.7554/eLife.64304
Liu, Yanyan ; Ke, Pu ; Kuo, Yi Chun ; Wang, Yuxiao ; Zhang, Xuewu ; Song, Chen ; Shan, Yibing. / A putative structural mechanism underlying the antithetic effect of homologous rnd1 and rhod gtpases in mammalian plexin regulation. In: eLife. 2021 ; Vol. 10.
@article{a83d6c333bdd4a09b52dc0f71facaf7b,
title = "A putative structural mechanism underlying the antithetic effect of homologous rnd1 and rhod gtpases in mammalian plexin regulation",
abstract = "Plexins are semaphorin receptors that play essential roles in mammalian neuronal axon guidance and in many other important mammalian biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism and is modulated by small GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations, we showed that RND1 reinforces the plexin dimerization interface, whereas RhoD destabilizes it due to their differential interaction with the cell membrane. Upon binding plexin at the Rho-GTPase-binding domain (RBD), RND1 and RhoD interact differently with the inner leaflet of the cell membrane and exert opposite effects on the dimerization interface via an allosteric network involving the RBD, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively charged membrane interface.",
author = "Yanyan Liu and Pu Ke and Kuo, {Yi Chun} and Yuxiao Wang and Xuewu Zhang and Chen Song and Yibing Shan",
note = "Funding Information: YL was supported by the National Natural Science Foundation of China (21806004) and Boya Post-doctoral Fellowship at Peking University. PK was supported by China NSAF Grant U1430237. XZ was supported in part by grants from the National institutes of Health (R35GM130289) and the Welch Foundation (I-1702). XZ is a Virginia Murchison Linthicum Scholar in Medical Research at UTSW. Results shown in this report are derived from work performed at the Argonne National Laboratory, Structural Biology Center at the Advance Photon Source. Argonne is operated by University of Chi-cago, Argonne for the US Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. CS was supported by the National Natural Science Foundation of China (21873006 and 32071251), and the Ministry of Science and Technology of China (2016YFA0500401). The MD simulations were performed on TianHe-1A at the National Supercom-puter Center in Tianjin, China. Funding Information: YL was supported by the National Natural Science Foundation of China (21806004) and Boya Postdoctoral Fellowship at Peking University. PK was supported by China NSAF Grant U1430237. XZ was supported in part by grants from the National institutes of Health (R35GM130289) and the Welch Foundation (I-1702). XZ is a Virginia Murchison Linthicum Scholar in Medical Research at UTSW. Results shown in this report are derived from work performed at the Argonne National Laboratory, Structural Biology Center at the Advance Photon Source. Argonne is operated by University of Chicago, Argonne for the US Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. CS was supported by the National Natural Science Foundation of China (21873006 and 32071251), and the Ministry of Science and Technology of China (2016YFA0500401). The MD simulations were performed on TianHe-1A at the National Supercomputer Center in Tianjin, China. Publisher Copyright: {\textcopyright} Liu et al.",
T1 - A putative structural mechanism underlying the antithetic effect of homologous rnd1 and rhod gtpases in mammalian plexin regulation
AU - Liu, Yanyan
AU - Ke, Pu
AU - Kuo, Yi Chun
AU - Wang, Yuxiao
AU - Zhang, Xuewu
AU - Song, Chen
AU - Shan, Yibing
N1 - Funding Information: YL was supported by the National Natural Science Foundation of China (21806004) and Boya Post-doctoral Fellowship at Peking University. PK was supported by China NSAF Grant U1430237. XZ was supported in part by grants from the National institutes of Health (R35GM130289) and the Welch Foundation (I-1702). XZ is a Virginia Murchison Linthicum Scholar in Medical Research at UTSW. Results shown in this report are derived from work performed at the Argonne National Laboratory, Structural Biology Center at the Advance Photon Source. Argonne is operated by University of Chi-cago, Argonne for the US Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. CS was supported by the National Natural Science Foundation of China (21873006 and 32071251), and the Ministry of Science and Technology of China (2016YFA0500401). The MD simulations were performed on TianHe-1A at the National Supercom-puter Center in Tianjin, China. Funding Information: YL was supported by the National Natural Science Foundation of China (21806004) and Boya Postdoctoral Fellowship at Peking University. PK was supported by China NSAF Grant U1430237. XZ was supported in part by grants from the National institutes of Health (R35GM130289) and the Welch Foundation (I-1702). XZ is a Virginia Murchison Linthicum Scholar in Medical Research at UTSW. Results shown in this report are derived from work performed at the Argonne National Laboratory, Structural Biology Center at the Advance Photon Source. Argonne is operated by University of Chicago, Argonne for the US Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. CS was supported by the National Natural Science Foundation of China (21873006 and 32071251), and the Ministry of Science and Technology of China (2016YFA0500401). The MD simulations were performed on TianHe-1A at the National Supercomputer Center in Tianjin, China. Publisher Copyright: © Liu et al.
N2 - Plexins are semaphorin receptors that play essential roles in mammalian neuronal axon guidance and in many other important mammalian biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism and is modulated by small GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations, we showed that RND1 reinforces the plexin dimerization interface, whereas RhoD destabilizes it due to their differential interaction with the cell membrane. Upon binding plexin at the Rho-GTPase-binding domain (RBD), RND1 and RhoD interact differently with the inner leaflet of the cell membrane and exert opposite effects on the dimerization interface via an allosteric network involving the RBD, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively charged membrane interface.
AB - Plexins are semaphorin receptors that play essential roles in mammalian neuronal axon guidance and in many other important mammalian biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism and is modulated by small GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations, we showed that RND1 reinforces the plexin dimerization interface, whereas RhoD destabilizes it due to their differential interaction with the cell membrane. Upon binding plexin at the Rho-GTPase-binding domain (RBD), RND1 and RhoD interact differently with the inner leaflet of the cell membrane and exert opposite effects on the dimerization interface via an allosteric network involving the RBD, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively charged membrane interface.