Dubna, Moscow, Russian Federation
Dubna, Moscow, Russian Federation
The occurrence of forward mutations in the arginine permease CAN1 gene, where damage leads to canavanine resistance, is often used to study mutagenesis in yeasts. We have obtained a representative collection of can1 mutations, which enables the mutational analysis of the arginine permease structure. This transport enzyme belongs to the APC superfamily supplying amino acids to cells. Despite sequence nonidentity, they have a similar structure. Eukaryotic arginine permease can serve as a model for the analysis of the structure and functioning of similar transporters. Studying arginine transport is of particular importance due to arginine being one of the key metabolites in nitrogen metabolism. Arginine is the NO-synthase substrate in NO synthesis, universal transmitter, neuromediator and actor of programmed cell death.
arginine permease, conveyors ARS-supersmash, mutational analysis of the structure of the enzyme
1. Kan M.J., Lee J.E., Wilson J.G., et al. Arginine deprivation and immune suppression in a mouse model of Alzheimer’s disease. The Journal of Neuroscience, 2015, vol. 35, pp. 5969-5982.
2. Opekarova M., Caspari T., Tanner W. Unidirectional arginine transport in reconstituted plasma-membrane vesicles from yeast overexpressing CAN1. European Journal of Biochemistry, 1993, vol. 211, pp. 683-688.
3. McCormick M.A., Delaney J.R., Tsuchiya M., Tsuchiyama S., Shemorry A., Sim S., Chou A.C., Ahmed U., Carr D., Murakami C.J., et al. A Comprehensive analysis of replicative lifespan in 4,698 single-gene deletion strains uncovers conserved mechanisms of aging. Cell Metabolism, 2015, vol. 22, pp. 895-906.
4. Ho B., Baryshnikova A., Brown G.W. Unification of protein abundance datasets yields a quantitative Saccharomyces cerevisiae proteome. Cell Systems, 2018, vol. 6, pp. 192-205.e3.
5. Malinska K., Malinsky J., Opekarova M., Tanner W. Distribution of Can1p into stable domains reflects lateral protein segregation within the plasma membrane of living Saccharomyces cerevisiae cells. Journal of Cell Science, 2004, vol. 117, pp. 6031-6041.
6. Bianchi F., Syga Ł., Moiset G., Spakman D., Schavemaker P.E., Punter C.M., Seinen A.B., van Oijen A.M., Robinson A., Poolman B. Steric exclusion and protein conformation determine the localization of plasma membrane transporters. Nature Communications, 2018, vol. 9, p. 501.
7. Walther T.C., Brickner J.H., Aguilar P.S., Bernales S., Pantoja C., Walter P. Eisosomes mark static sites of endocytosis. Nature, 2006, vol. 439, pp. 998-1003.
8. Yofe I., Weill U., Meurer M., Chuartzman S., Zalckvar E., Goldman O., Ben-Dor S., Schütze C., Wiedemann N., Knop M., Khmelinskii A., Schuldiner M. One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy. Nature Methods, 2016, vol. 13, pp. 371-378.
9. Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R., Meyer H.E., Schönfisch B., Perschil I., Chacinska A., Guiard B., Rehling P., Pfanner N., Meisinger C. The proteome of Saccharomyces cerevisiae mitochondria. Proceedings of National Academy of Sciences of the USA, 2003, vol. 100, pp. 13207-13212.
10. Reinders J., Zahedi R.P., Pfanner N., Meisinger C., Sickmann A., et al. Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics. Journal of Proteome Reserch, 2006, vol. 5, pp. 1543-1554.
11. Gao X., Zhou L., Shi Y. Structure of Arg-bound Escherichia coli AdiC. Nature, 2010, vol. 463, pp. 828-832.
12. Kowalczyk L., Ratera M., Paladino A., Bartocciono A., Errasti-Murugarren E., Valencia E., Portella G., Bial S., Zorzano A., Fita I., Orozco M., Carpena X., Vazquez-Ibar J.L., Palacin M. Molecular basis of substrate-induced permeation by an amino acid antiporter. Proceedings of National Academy of Sciences of the USA, 2011, vol. 108, pp. 3935-3940.
13. Ilgue H., Jeckelmann J.M., Gapsys V., Ucurum Z., de Groot B.L., Fotiadis D. Insight into the molecular basis for substrate binding and specificity of the wild-type L-arginine/agmatine antiporter AdiC. Proceedings of National Academy of Sciences of the USA, 2016, vol. 113, pp. 10358-10363.
14. Ma D., Lu P.L., Yan C.Y., Fan C., Yin P., Wang J.W., Shi Y.G. Structure and mechanism of a glutamate-GABA antiporter. Nature, 2012, vol. 483, pp. 632-636.
15. Shaffer P.L., Goehring A.S., Shankaranarayanan A., Gouaux E. Structure and mechanism of a Na+ -independent amino acid transporter. Science, 2009, vol. 325, pp. 1010-1014.
16. Jungnickel K.E.J., Newstead S. Crystal structure of a bacterial cationic amino acid transporter (CAT) homologue bound to Arginine. Nature Communications, 2018, vol. 9, pp. 550-550.
17. Humphrey W., Dalke A., Schulten K. VMD - Visual Molecular Dynamics. Journal of Molecular Graphics, 1996, vol. 14, pp. 33-38.
18. Šali A., Blundell T.L.Comparative protein modeling by satisfaction of spatial restraints. Journal of Molecular Biology, 1993, vol. 234, pp. 779-815.
19. Ghaddar K., Krammer E.-M., Mihajlovic N., Brohée S., André B., Prévost M. Converting the yeast arginine Can1 permease to a lysine permease. Journal of Biological Chemistry, 2014, vol. 289, pp. 7232-7246.
20. Swaney D.L., Beltrao P., Starita L., Guo A., Rush J., Fields S., Krogan N.J., Villén J. Global analysis of phosphorylation and ubiquitylation cross-talk in protein degradation. Nature Methods, 2013, vol. 10, pp. 676-682.
21. Kolawa N., Sweredoski M.J., Graham R.L., Oania R., Hess S., Deshaies R.J. Perturbations to the ubiquitin conjugate proteome in yeast δubx mutants identify Ubx2 as a regulator of membrane lipid composition. Molecular & Cellular Proteomics, 2013, vol. 12, pp. 2791-2803.
22. Fang N.N., Chan G.T., Zhu M., Comyn S.A., Persaud A., Deshaies R.J., Rotin D., Gsponer J., Mayor T. Rsp5/Nedd4 is the main ubiquitin ligase that targets cytosolic misfolded proteins following heat stress. Nature Cell Biology, 2014, vol. 16, pp. 1227-1237.
23. Soulard A., Cremonesi A., Moes S., Schütz F., Jenö P., Hall M.N.l. The rapamycin-sensitive phosphoproteome reveals that TOR controls protein kinase A toward some but not all substrates. Molecular Biology of the Cell, 2010, vol. 21, pp. 3475-3486.
24. Holt L.J., Tuch B.B., Villén J., Johnson A.D., Gygi S.P., Morgan D.O. Global analysis of Cdk1 substrate phosphorylation sites provides insights into evolution. Science, 2009, vol. 325, pp. 1682-1686.
25. Lauwers E., Erpapazoglou Z., Haguenauer-Tsapis R., Andre B. The ubiquitin code of yeast permease trafficking. Trends in Cell Biology, 2010, vol. 20, pp. 196-204.
26. Becuwe M., Herrador A., Haguenauer-Tsapis R., Vincent O., Leon S. Ubiquitin-mediated regulation of endocytosis by proteins of the arrestin family. Biochemistry Research International, 2012, 242764. DOI:https://doi.org/10.1155/2012/242764.
27. Ghaddar K., Merhl A., Saliba E., Krammer E.-M., Prevost M., Andre B. Substrate-induced ubiquitylation and endocytosus of yeast amino acid permeases. Molecular and Cellular Biology, 2014, vol. 34, pp. 4447-4463.
28. Keener J.M., Babst M. Quality control and substrate-dependent doqnregulatio of the nutrient transporter Fur4. Traffic, 2013, vol. 14, pp. 412-427.
29. Lin C.H., MacGurn J.A., Chu T., Stefan C.J., Emr S.D. Arrestin-related ubiquitin-ligase adaptors regulate endocytosis and protein turnover at the cell surface. Cell, 2008, vol. 135, pp. 714-725.
