Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1998 Feb 16;17(4):977–984. doi: 10.1093/emboj/17.4.977

Synapsin I is structurally similar to ATP-utilizing enzymes.

L Esser 1, C R Wang 1, M Hosaka 1, C S Smagula 1, T C Südhof 1, J Deisenhofer 1
PMCID: PMC1170447  PMID: 9463376

Abstract

Synapsins are abundant synaptic vesicle proteins with an essential regulatory function in the nerve terminal. We determined the crystal structure of a fragment (synC) consisting of residues 110-420 of bovine synapsin I; synC coincides with the large middle domain (C-domain), the most conserved domain of synapsins. SynC molecules are folded into compact domains and form closely associated dimers. SynC monomers are strikingly similar in structure to a family of ATP-utilizing enzymes, which includes glutathione synthetase and D-alanine:D-alanine ligase. SynC binds ATP in a Ca2+-dependent manner. The crystal structure of synC in complex with ATPgammaS and Ca2+ explains the preference of synC for Ca2+ over Mg2+. Our results suggest that synapsins may also be ATP-utilizing enzymes.

Full Text

The Full Text of this article is available as a PDF (537.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Artymiuk P. J., Poirrette A. R., Rice D. W., Willett P. Biotin carboxylase comes into the fold. Nat Struct Biol. 1996 Feb;3(2):128–132. doi: 10.1038/nsb0296-128. [DOI] [PubMed] [Google Scholar]
  2. Baines A. J., Bennett V. Synapsin I is a microtubule-bundling protein. Nature. 1986 Jan 9;319(6049):145–147. doi: 10.1038/319145a0. [DOI] [PubMed] [Google Scholar]
  3. Baines A. J., Bennett V. Synapsin I is a spectrin-binding protein immunologically related to erythrocyte protein 4.1. 1985 May 30-Jun 5Nature. 315(6018):410–413. doi: 10.1038/315410a0. [DOI] [PubMed] [Google Scholar]
  4. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  5. Bähler M., Greengard P. Synapsin I bundles F-actin in a phosphorylation-dependent manner. Nature. 1987 Apr 16;326(6114):704–707. doi: 10.1038/326704a0. [DOI] [PubMed] [Google Scholar]
  6. Cowtan K. D., Main P. Phase combination and cross validation in iterated density-modification calculations. Acta Crystallogr D Biol Crystallogr. 1996 Jan 1;52(Pt 1):43–48. doi: 10.1107/S090744499500761X. [DOI] [PubMed] [Google Scholar]
  7. Falke J. J., Drake S. K., Hazard A. L., Peersen O. B. Molecular tuning of ion binding to calcium signaling proteins. Q Rev Biophys. 1994 Aug;27(3):219–290. doi: 10.1017/s0033583500003012. [DOI] [PubMed] [Google Scholar]
  8. Fan C., Moews P. C., Walsh C. T., Knox J. R. Vancomycin resistance: structure of D-alanine:D-alanine ligase at 2.3 A resolution. Science. 1994 Oct 21;266(5184):439–443. doi: 10.1126/science.7939684. [DOI] [PubMed] [Google Scholar]
  9. Flaherty K. M., Wilbanks S. M., DeLuca-Flaherty C., McKay D. B. Structural basis of the 70-kilodalton heat shock cognate protein ATP hydrolytic activity. II. Structure of the active site with ADP or ATP bound to wild type and mutant ATPase fragment. J Biol Chem. 1994 Apr 29;269(17):12899–12907. [PubMed] [Google Scholar]
  10. Greengard P. Neuronal phosphoproteins. Mediators of signal transduction. Mol Neurobiol. 1987 Spring-Summer;1(1-2):81–119. doi: 10.1007/BF02935265. [DOI] [PubMed] [Google Scholar]
  11. Hayes N. V., Bennett A. F., Baines A. J. Selective Ca2(+)-dependent interaction of calmodulin with the head domain of synapsin 1. Biochem J. 1991 Apr 1;275(Pt 1):93–97. doi: 10.1042/bj2750093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Herzberg O., Chen C. C., Kapadia G., McGuire M., Carroll L. J., Noh S. J., Dunaway-Mariano D. Swiveling-domain mechanism for enzymatic phosphotransfer between remote reaction sites. Proc Natl Acad Sci U S A. 1996 Apr 2;93(7):2652–2657. doi: 10.1073/pnas.93.7.2652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Holm L., Sander C. Protein structure comparison by alignment of distance matrices. J Mol Biol. 1993 Sep 5;233(1):123–138. doi: 10.1006/jmbi.1993.1489. [DOI] [PubMed] [Google Scholar]
  14. Inui M., Watanabe T., Sobue K. Annexin VI binds to a synaptic vesicle protein, synapsin I. J Neurochem. 1994 Nov;63(5):1917–1923. doi: 10.1046/j.1471-4159.1994.63051917.x. [DOI] [PubMed] [Google Scholar]
  15. Jones T. A., Zou J. Y., Cowan S. W., Kjeldgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991 Mar 1;47(Pt 2):110–119. doi: 10.1107/s0108767390010224. [DOI] [PubMed] [Google Scholar]
  16. Kahn D. W., Besterman J. M. Cytosolic rat brain synapsin I is a diacylglycerol kinase. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6137–6141. doi: 10.1073/pnas.88.14.6137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Klagges B. R., Heimbeck G., Godenschwege T. A., Hofbauer A., Pflugfelder G. O., Reifegerste R., Reisch D., Schaupp M., Buchner S., Buchner E. Invertebrate synapsins: a single gene codes for several isoforms in Drosophila. J Neurosci. 1996 May 15;16(10):3154–3165. doi: 10.1523/JNEUROSCI.16-10-03154.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matsuda K., Mizuguchi K., Nishioka T., Kato H., Go N., Oda J. Crystal structure of glutathione synthetase at optimal pH: domain architecture and structural similarity with other proteins. Protein Eng. 1996 Dec;9(12):1083–1092. doi: 10.1093/protein/9.12.1083. [DOI] [PubMed] [Google Scholar]
  19. McPherson P. S., Czernik A. J., Chilcote T. J., Onofri F., Benfenati F., Greengard P., Schlessinger J., De Camilli P. Interaction of Grb2 via its Src homology 3 domains with synaptic proteins including synapsin I. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6486–6490. doi: 10.1073/pnas.91.14.6486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mizutani A., Tokumitsu H., Hidaka H. Acidic calmodulin binding protein, ACAMP-81, is MARCKS protein interacting with synapsin I. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1395–1401. doi: 10.1016/0006-291x(92)91888-w. [DOI] [PubMed] [Google Scholar]
  21. Murzin A. G., Brenner S. E., Hubbard T., Chothia C. SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol. 1995 Apr 7;247(4):536–540. doi: 10.1006/jmbi.1995.0159. [DOI] [PubMed] [Google Scholar]
  22. Petrucci T. C., Morrow J. S. Synapsin I: an actin-bundling protein under phosphorylation control. J Cell Biol. 1987 Sep;105(3):1355–1363. doi: 10.1083/jcb.105.3.1355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rosahl T. W., Geppert M., Spillane D., Herz J., Hammer R. E., Malenka R. C., Südhof T. C. Short-term synaptic plasticity is altered in mice lacking synapsin I. Cell. 1993 Nov 19;75(4):661–670. doi: 10.1016/0092-8674(93)90487-b. [DOI] [PubMed] [Google Scholar]
  24. Rosahl T. W., Spillane D., Missler M., Herz J., Selig D. K., Wolff J. R., Hammer R. E., Malenka R. C., Südhof T. C. Essential functions of synapsins I and II in synaptic vesicle regulation. Nature. 1995 Jun 8;375(6531):488–493. doi: 10.1038/375488a0. [DOI] [PubMed] [Google Scholar]
  25. Sriram M., Osipiuk J., Freeman B., Morimoto R., Joachimiak A. Human Hsp70 molecular chaperone binds two calcium ions within the ATPase domain. Structure. 1997 Mar 15;5(3):403–414. doi: 10.1016/s0969-2126(97)00197-4. [DOI] [PubMed] [Google Scholar]
  26. Steiner J. P., Ling E., Bennett V. Nearest neighbor analysis for brain synapsin I. Evidence from in vitro reassociation assays for association with membrane protein(s) and the Mr = 68,000 neurofilament subunit. J Biol Chem. 1987 Jan 15;262(2):905–914. [PubMed] [Google Scholar]
  27. Südhof T. C., Czernik A. J., Kao H. T., Takei K., Johnston P. A., Horiuchi A., Kanazir S. D., Wagner M. A., Perin M. S., De Camilli P. Synapsins: mosaics of shared and individual domains in a family of synaptic vesicle phosphoproteins. Science. 1989 Sep 29;245(4925):1474–1480. doi: 10.1126/science.2506642. [DOI] [PubMed] [Google Scholar]
  28. Südhof T. C. The synaptic vesicle cycle: a cascade of protein-protein interactions. Nature. 1995 Jun 22;375(6533):645–653. doi: 10.1038/375645a0. [DOI] [PubMed] [Google Scholar]
  29. Tanaka T., Kato H., Nishioka T., Oda J. Mutational and proteolytic studies on a flexible loop in glutathione synthetase from Escherichia coli B: the loop and arginine 233 are critical for the catalytic reaction. Biochemistry. 1992 Mar 3;31(8):2259–2265. doi: 10.1021/bi00123a007. [DOI] [PubMed] [Google Scholar]
  30. Waldrop G. L., Rayment I., Holden H. M. Three-dimensional structure of the biotin carboxylase subunit of acetyl-CoA carboxylase. Biochemistry. 1994 Aug 30;33(34):10249–10256. doi: 10.1021/bi00200a004. [DOI] [PubMed] [Google Scholar]
  31. Wang C. R., Esser L., Smagula C. S., Südhof T. C., Deisenhofer J. Identification, expression, and crystallization of the protease-resistant conserved domain of synapsin I. Protein Sci. 1997 Oct;6(10):2264–2267. doi: 10.1002/pro.5560061022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wolodko W. T., Fraser M. E., James M. N., Bridger W. A. The crystal structure of succinyl-CoA synthetase from Escherichia coli at 2.5-A resolution. J Biol Chem. 1994 Apr 8;269(14):10883–10890. doi: 10.2210/pdb1scu/pdb. [DOI] [PubMed] [Google Scholar]
  33. Yamaguchi H., Kato H., Hata Y., Nishioka T., Kimura A., Oda J., Katsube Y. Three-dimensional structure of the glutathione synthetase from Escherichia coli B at 2.0 A resolution. J Mol Biol. 1993 Feb 20;229(4):1083–1100. doi: 10.1006/jmbi.1993.1106. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES