A salt bridge linking the first intracellular loop with the C terminus facilitates the folding of the serotonin transporter

Journal of Biological Chemistry

Volumn 290, Issue 21, 2015, Pages 13263-13278

  Koban, Florian ^a   El Kasaby, Ali ^a,b   Häusler, Cornelia ^a   Stockner, Thomas ^a   Simbrunner, Benedikt M ^a   Sitte, Harald H ^a   Freissmuth, Michael ^a   Sucic, Sonja ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b Mansoura University   (Egypt)

Author keywords

[No Author keywords available]

Indexed keywords

FACINGS; RESTORATION;

CELL SURFACE EXPRESSION; CONFORMATIONAL SEARCH; ENDOPLASMIC RETICULUM; FIRST INTRACELLULAR LOOPS; INTRACELLULAR LOOP; MECHANISTIC MODELING; SEROTONIN TRANSPORTERS; SURFACE EXPRESSION;

CELL MEMBRANES;

INTERLEUKIN 1; SEROTONIN TRANSPORTER;

ALPHA HELIX; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELLULAR DISTRIBUTION; CONTROLLED STUDY; ENDOPLASMIC RETICULUM; HYDROPHOBICITY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN INTERACTION; PROTEIN STABILITY; PROTEIN TRANSPORT; SEQUENCE ALIGNMENT; CELL MEMBRANE; CHEMICAL STRUCTURE; CHEMISTRY; CONFOCAL MICROSCOPY; GENETICS; HEK293 CELL LINE; HUMAN; METABOLISM; MUTATION; PROTEIN TERTIARY STRUCTURE; SITE DIRECTED MUTAGENESIS; WESTERN BLOTTING;

BLOTTING, WESTERN; CELL MEMBRANE; ENDOPLASMIC RETICULUM; HEK293 CELLS; HUMANS; MICROSCOPY, CONFOCAL; MODELS, MOLECULAR; MUTAGENESIS, SITE-DIRECTED; MUTATION; PROTEIN FOLDING; PROTEIN STRUCTURE, TERTIARY; PROTEIN TRANSPORT; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS;

EID: 84929990569     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.641357     Document Type: Article

References (48)

1. Sucic, S., El-Kasaby, A., Kudlacek, O., Sarker, S., Sitte, H. H., Marin, P., and Freissmuth, M. (2011) The serotonin transporter is an exclusive client of the coat protein complex II (COPII) component SEC24C. J. Biol. Chem. 286, 16482-16490
2. Sucic, S., Koban, F., El-Kasaby, A., Kudlacek, O., Stockner, T., Sitte, H. H., and Freissmuth, M. (2013) Switching the clientele: a lysine residing in the C terminus of the serotonin transporter specifies its preference for the coat protein complex II component SEC24C. J. Biol. Chem. 288, 5330-5341
3. Montgomery, T. R., Steinkellner, T., Sucic, S., Koban, F., Schüchner, S., Ogris, E., Sitte, H. H., and Freissmuth, M. (2014) Axonal targeting of the serotonin transporter in cultured rat dorsal raphe neurons is specified by SEC24C-dependent export from the endoplasmic reticulum. J. Neurosci. 34, 6344-6351
4. El-Kasaby, A., Just, H., Malle, E., Stolt-Bergner, P. C., Sitte, H. H., Freissmuth, M., and Kudlacek, O. (2010) Mutations in the carboxyl-terminal SEC24 binding motif of the serotonin transporter impair folding of the transporter. J. Biol. Chem. 285, 39201-39210
5. El-Kasaby, A., Koban, F., Sitte, H. H., Freissmuth, M., and Sucic, S. (2014) A cytosolic relay of heat shock proteins HSP70-1A and HSP90β monitors the folding trajectory of the serotonin transporter. J. Biol. Chem. 289, 28987-29000
6. Jacobs, M. T., Zhang, Y. W., Campbell, S. D., and Rudnick, G. (2007) Ibogaine, a noncompetitive inhibitor of serotonin transport, acts by stabilizing the cytoplasm-facing state of the transporter. J. Biol. Chem. 282, 29441-29447
7. Bulling, S., Schicker, K., Zhang, Y. W., Steinkellner, T., Stockner, T., Gruber, C. W., Boehm, S., Freissmuth, M., Rudnick, G., Sitte, H. H., and Sandtner, W. (2012) The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. J. Biol. Chem. 287, 18524-18534
8. Chiba, P., Freissmuth, M., and Stockner, T. (2014) Defining the blanks - pharmacochaperoning of SLC6 transporters and ABC transporters. Pharmacol. Res. 83, 63-73
9. Kurian, M. A., Zhen, J., Cheng, S. Y., Li, Y., Mordekar, S. R., Jardine, P., Morgan, N. V., Meyer, E., Tee, L., Pasha, S., Wassmer, E., Heales, S. J., Gissen, P., Reith, M. E., and Maher, E. R. (2009) Homozygous loss-of-function mutations in the gene encoding the dopamine transporter are associated with infantile parkinsonism-dystonia. J. Clin. Investig. 119, 1595-1603
10. Kurian, M. A., Li, Y., Zhen, J., Meyer, E., Hai, N., Christen, H. J., Hoffmann, G. F., Jardine, P., von Moers, A., Mordekar, S. R., O'Callaghan, F., Wassmer, E., Wraige, E., Dietrich, C., Lewis, T., Hyland, K., Heales, S., Jr., Sanger, T., Gissen, P., Assmann, B. E., Reith, M. E., and Maher, E. R. (2011) Clinical and molecular characterisation of hereditary dopamine transporter deficiency syndrome: an observational cohort and experimental study. Lancet Neurol. 10, 54-62
11. Ng, J., Zhen, J., Meyer, E., Erreger, K., Li, Y., Kakar, N., Ahmad, J., Thiele, H., Kubisch, C., Rider, N. L., Morton, D. H., Strauss, K. A., Puffenberger, E. G., D'Agnano, D., Anikster, Y., Carducci, C., Hyland, K., Rotstein, M., Leuzzi, V., Borck, G., Reith, M. E., and Kurian, M. A. (2014) Dopamine transporter deficiency syndrome: phenotypic spectrum from infancy to adulthood. Brain 137, 1107-1119
12. Rees, M. I., Harvey, K., Pearce, B. R., Chung, S. K., Duguid, I. C., Thomas, P., Beatty, S., Graham, G. E., Armstrong, L., Shiang, R., Abbott, K. J., Zuberi, S. M., Stephenson, J. B., Owen, M. J., Tijssen, M. A., van den Maagdenberg, A. M., Smart, T. G., Supplisson, S., and Harvey, R. J. (2006) Mutations in the gene encoding GlyT2 (SLC6A5) define a presynaptic component of human startle disease. Nat. Genet. 38, 801-806
13. Carta, E., Chung, S. K., James, V. M., Robinson, A., Gill, J. L., Remy, N., Vanbellinghen, J. F., Drew, C. J., Cagdas, S., Cameron, D., Cowan, F. M., Del Toro, M., Graham, G. E., Manzur, A. Y., Masri, A., Rivera, S., Scalais, E., Shiang, R., Sinclair, K., Stuart, C. A., Tijssen, M. A., Wise, G., Zuberi, S. M., Harvey, K., Pearce, B. R., Topf, M., Thomas, R. H., Supplisson, S., Rees, M. I., and Harvey, R. J. (2012) Mutations in the GlyT2 gene (SLC6A5) are a second major cause of startle disease. J. Biol. Chem. 287, 28975-28985
14. Arribas-González, E., de Juan-Sanz, J., Aragón, C., and López-Corcuera, B. (2015) Molecular basis of the dominant-negative effect of a glycine transporter 2 mutation associated with hyperekplexia. J. Biol. Chem. 290, 2150-2165
15. Hohenegger, M., Mitterauer, T., Voss, T., Nanoff, C., and Freissmuth, M. (1996) Thiophosphorylation of the G protein β-subunit in human platelet membranes: evidence against a direct phosphate transfer reaction to Gα subunits. Mol. Pharmacol. 49, 73-80
16. Edgar, R. C. (2004) MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5, 113
17. Stockner, T., Montgomery, T. R., Kudlacek, O., Weissensteiner, R., Ecker, G. F., Freissmuth, M., and Sitte, H. H. (2013) Mutational analysis of the high-affinity zinc binding site validates a refined human dopamine transporter homology model. PLoS Comput. Biol. 9, e1002909
18. Penmatsa, A., Wang, K. H., and Gouaux, E. (2013) X-ray structure of dopamine transporter elucidates antidepressant mechanism. Nature 503, 85-90
19. Sali, A., and Blundell, T. L. (1993) Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 234, 779-815
20. Shen, M. Y., and Sali, A. (2006) Statistical potential for assessment and prediction of protein structures. Protein Sci. 15, 2507-2524
21. Wolf, M. G., Hoefling, M., Aponte-Santamaría, C., Grubmüller, H., and Groenhof, G. (2010) g-membed: efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation. J. Comput. Chem. 31, 2169-2174
22. Hess, B., Kutzner, C., van der Spoel, D., and Lindahl, E. (2008) GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 4, 435-447
23. Jorgensen, W. L., Maxwell, D. S., and Tirado-Rives, J. (1996) Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 118, 11225-11236
24. Berger, O., Edholm, O., and Jähnig, F. (1997) Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys. J. 72, 2002-2013
25. Hess, B., Bekker, H., Berendsen, H. J., and Fraaije, J. G. (1997) LINCS: a linear constraint solver for molecular simulations. J. Comput. Chem. 18, 1463-1472
26. Bussi, G., Donadio, D., and Parrinello, M. (2007) Canonical sampling through velocity rescaling. J. Chem. Phys. 126, 014101
27. Berendsen, H. J., Postma, J. P., van Gunsteren, W. F., DiNola, A., and Haak, J. R. (1984) Molecular dynamics with coupling to an external bath. J. Chem. Phys. 81, 3684
28. Darden, T., York, D., and Pedersen, L. (1993) Particle mesh Ewald: an N·log(N) method for Ewald sums in large systems. J. Chem. Phys. 98, 10089
29. Fenollar-Ferrer, C., Stockner, T., Schwarz, T. C., Pal, A., Gotovina, J., Hofmaier, T., Jayaraman, K., Adhikary, S., Kudlacek, O., Mehdipour, A. R., Tavoulari, S., Rudnick, G., Singh, S. K., Konrat, R., Sitte, H. H., and Forrest, L. R. (2014) Structure and regulatory interactions of the cytoplasmic terminal domains of serotonin transporter. Biochemistry 53, 5444-5460
30. Chakrabartty, A., Kortemme, T., and Baldwin, R. L. (1994) Helix propensities of the amino acids measured in alanine-based peptides without helix-stabilizing side-chain interactions. Protein Sci. 3, 843-852
31. Pace, C. N., and Scholtz, J. M. (1998) A helix propensity scale based on experimental studies of peptides and proteins. Biophys. J. 75, 422-427
32. Miller, E., Antonny, B., Hamamoto, S., and Schekman, R. (2002) Cargo selection into COPII vesicles is driven by the Sec24p subunit. EMBO J. 21, 6105-6113
33. Farhan, H., Reiterer, V., Korkhov, V. M., Schmid, J. A., Freissmuth, M., and Sitte, H. H. (2007) Concentrative export from the endoplasmic reticulum of the γ-aminobutyric acid transporter 1 requires binding to SEC24D. J. Biol. Chem. 282, 7679-7689
34. Korkhov, V. M., Holy, M., Freissmuth, M., and Sitte, H. H. (2006) The conserved glutamate (Glu136) in transmembrane domain 2 of the serotonin transporter is required for the conformational switch in the transport cycle. J. Biol. Chem. 281, 13439-13448
35. Sucic, S., Dallinger, S., Zdrazil, B., Weissensteiner, R., Jørgensen, T. N., Holy, M., Kudlacek, O., Seidel, S., Cha, J. H., Gether, U., Newman, A. H., Ecker, G. F., Freissmuth, M., and Sitte, H. H. (2010) The amino terminus of monoamine transporters is a lever required for the action of amphetamines. J. Biol. Chem. 285, 10924-10938
36. Qi, Y., Wang, J. K., McMillian, M., and Chikaraishi, D. M. (1997) Characterization of a CNS cell line, CAD, in which morphological differentiation is initiated by serum deprivation. J. Neurosci. 17, 1217-1225
37. Reiterer, V., Maier, S., Sitte, H. H., Kriz, A., Rüegg, M. A., Hauri, H. P., Freissmuth, M., and Farhan, H. (2008) Sec24- and ARFGAP1-dependent trafficking of GABA transporter-1 is a prerequisite for correct axonal targeting. J. Neurosci. 28, 12453-12464
38. Hartl, F. U., Bracher, A., and Hayer-Hartl, M. (2011) Molecular chaperones in protein folding and proteostasis. Nature 475, 324-332
39. Jahn, T. R., and Radford, S. E. (2005) The Yin and Yang of protein folding. FEBS J. 272, 5962-5970
40. Vashist, S., and Ng, D. T. (2004) Misfolded proteins are sorted by a sequential checkpoint mechanism of ER quality control. J. Cell Biol. 165, 41-52
41. Houck, S. A., and Cyr, D. M. (2012) Mechanisms for quality control of misfolded transmembrane proteins. Biochim. Biophys. Acta 1818, 1108-1114
42. Yamashita, A., Singh, S. K., Kawate, T., Jin, Y., and Gouaux, E. (2005) Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters. Nature 437, 215-223
43. Krishnamurthy, H., and Gouaux, E. (2012) X-ray structures of LeuT in substrate-free outward-open and apo inward-open states. Nature 481, 469-474
44. Larsen, M. B., Fjorback, A. W., and Wiborg, O. (2006) The C-terminus is critical for the functional expression of the human serotonin transporter. Biochemistry 45, 1331-1337
45. Bergmayr, C., Thurner, P., Keuerleber, S., Kudlacek, O., Nanoff, C., Freissmuth, M., and Gruber, C. W. (2013) Recruitment of a cytoplasmic chaperone relay by the A2A-adenosine receptor. J. Biol. Chem. 288, 28831-28844
46. Pankevych, H., Korkhov, V., Freissmuth, M., and Nanoff, C. (2003) Truncation of the A1-adenosine receptor reveals distinct roles of the membrane-proximal carboxy terminus in receptor folding and G protein coupling. J. Biol. Chem. 278, 30283-30293
47. Málaga-Diéguez, L., Yang, Q., Bauer, J., Pankevych, H., Freissmuth, M., and Nanoff, C. (2010) Pharmacochaperoning of the A1 adenosine receptor is contingent upon the endoplasmic reticulum. Mol. Pharmacol. 77, 940-952
48. Kusek, J., Yang, Q., Witek, M., Gruber, C. W., Nanoff, C., and Freissmuth, M. (2015) Chaperoning of the A1-adenosine receptor by endogenous adenosine-an extension of the retaliatory metabolite concept. Mol. Pharmacol. 87, 39-51