Cómo citar
Descargas
Métricas Alternativas
Dimensions
Resumen
La determinación de los dominios proteicos transmembranales sigue siendo un problema no completamente resuelto dentro de la química de las proteínas. Al grupo de proteínas de membrana pertenecen importantes estructuras entre las que se encuentra el receptor ionotrópico de glutamato activado por N-metil-aspartato, tópico del presente trabajo. Esta proteína multiheteromérica se encuentra involucrada en importantes eventos fisiológicos, así como en muchas entidades patológicas. Una mejor comprensión de las propiedades de su secuencia y de su estructura ayudarán para una mejor comprensión de sus distintos roles y para unas mejores aproximaciones en el diseño de drogas para tratar los desordenes en los que está involucrado. En el presente trabajo se predicen las secuencias que hacen parte de todas las regiones transmembranales de las diferentes subunidades constituyentes del receptor por medio de diversos algoritmos para finalmente generar una predicción de consenso. Se comparan las predicciones con los pocos datos experimentales previamente publicados encontrándose una alta calidad de las predicciones.
Palabras clave
Citas
Abdeddaïm, S. & B. Morgenstern. 2001. Speeding up the DIALIGN multiple alignment program by using the ‘Greedy Alignment of BIOlogical Sequences LIBrary’ GABIOS-LIB. Lecture Notes in Computer Science 2066: 1-11.
Andersson, O., A. Stenqvist, A. Attersand & G. von Euler. 2001. Nucleotide sequence, genomic organization, and chromosomal localization of genes encoding the human NMDA receptor subunits NR3A and NR3B. Genomics 78: 178-184.
Arden, S. R., J. R., Sinor, W. K. Potthoff, & E. Aizenman. 1998. Subunit-specificiy interactions of cyanide with the N-Methyl-D-Aspartate receptor. J. Biol. Chem., 273: 21505-21511.
Arora, A. & L. K. Tamm. 2001. Biophysical approaches to membrane protein structure determination. Curr. Opin. Struct. Boil. 11:540-547.
Berman, H. M., J., Westbrook, Z., Feng, G., Gilliland, T. N.,
Bhat, H., Weissig, I. N. Shindyalov & P. E. Bourne. 2000. The Protein Data Bank. Nucleic Acids Research, 28: 235-242.
Blahos, J. & R. J. Wenthold. 1996. Relationship between N-methylD-Aspartate receptor NR1 splice variants and NR2 subunits. J. Biol. Chem. 271: 15669-15674.
Brendel, V., P., Bucher, I. R., Nourbakhsh, B. E. Blaisdell, S. Karlin. 1992. Methods and Algorithms for Statistical Analysis of Protein Sequences. Proc. Natl. Acad. Sci. USA, 89: 2002-2006.
Briecombe, J. C., F. A. Boeckman & E. Aizenman. 1997. Functional consequences of NR2 subunit composition in single recombinant N-Methyl-D-Aspartate receptors. Proc. Natl. Acad. Sci. USA, 94: 11019-11024.
Chen, C. & B. Rost. 2002. State-of-the-art membrane protein prediction. Applied Bioinformatics 1: 21-35.
Claros, M. G., & G. von Heijne. 1994. TopPred II: An Improved Software For Membrane Protein Structure Predictions. CABIOS 10: 685-686.
Cochilla, A. J. & S. Alford. 1999. NMDA receptor-mediated control of presynaptic calcium and neurotransmitter release. J. Neuroscience 19:193-205.
Cserzo, M., E., Wallin, I., Simon, G. von Heijne & A. Elofsson. 1997. Prediction of transmembrane alpha-helices in procariotic membrane proteins: the Dense Alignment Surface method. Prot. Eng. 10: 673-676.
Cushing, A., M. J., Price-Jones, R., Graves, A. J., Harris, K. T., Hughes, D. Bleakman & D. Lodge. 1999. Measurement of calcium flux through ionotropic glutamate receptors using Cytostar-T scintillating microplates. J. Neurosc. Meth. 90:33-36.
Eisenberg, D., Weiss, R. M. & Trwilliger, T. C. 1982. The helical hydrophobic moment: a measure of the amphiphilicity of a helix. Nature 299:371-374.
Ferrer-Montiel, A. V. & Montal, M. 1996. Pentameric subunit stoichiometry of a neuronal glutamate receptor. Proc. Natl. Acad. Sci. USA, 93: 2741-2744.
Franciolini, F. & A. Petris, 1989. Evolution of ionic channels of biological membranes. Mol. Biol. Evol. 6: 503-513.
Hawkins, L. H., P. L. Chazot & F. A. Stephenson. 1999. Biochemical evidence for the co-association of three N-methyl-D-aspartate NMDA. R2 subunits in recombinant NMDA receptors. J. Biol. Chem. 274: 27211-27218.
Higgins, D., J. Thompson, T. Gibson, J. D. Thompson, D.G. Higgins & T. J. Gibson 1994. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22:4673-4680.
Hirai, H., J. Kirsch, B. Laube, H. Betz & J. Kuhse. 1996. The glycine binding site of the N-methyl-D-aspartate receptor subunit NR1, identification of novel determinants of co-agonist potentiation in the extracellular M3-M4 loop region. Proc. Nat. Acad. Sci. USA, 93: 6031-6036.
Hoffmann, K. & W. Stoffel. 1993. TMbase - A database of membrane spanning proteins segments. Biol. Chem. Hoppe-Seyler 374:166-168.
Hollman, M. 1999. Structure of ionotropic glutamate receptors. In: P. Jonas & Monyer, H., Eds. Ionotropic glutamate receptors in the CNS. Berlin: Springer-Verlag, pp. 3-98.
Honer, M., D. Benke, B.Laube, J. Kuhse, R. Heckendorn, H. Allgeiers, C. Angst, H. Monyer, P. T. Seeburg, H. Betz & H. Mohler. 1998. Differentiation of glycine antagonist sites of N-methyl-D-Aspartate receptor subtypes. J. Biol. Chem. 273: 11158-11163.
Jennings, M. L. 1989. Topography of membrane proteins. Annu. Rev. Biochem. 58: 999-1027.
Kashiwagi, K., A. J. Pahk, T. Masuko, K. Igarashi & K. Williams. 1997. Block and modulation of N-methyl-D-aspartate receptors by polyamines and protons, role of amino acid residues in the transmembrane and pore-forming regions of NR1 and NR2 subunits. Mol. Pharm. 52: 701-713.
Krogh, A., B. Larsson, G. von Heijne & E. Sonnhammer. 2001. Prediction of transmembrane protein topology with a Hidden Markov Model: Application to complete genomes. J. Mol. Biol. 305: 567-580.
Kyte, J. & R. F. Doolittle. 1982. A simple method for displaying the hydropathic character of a protein. J. Mol. Biol. 157: 105-132.
Laube, B., J. Kuhse, & H. Betz. 1998. Evidence for a tetrameric structure of recombinant NMDA receptor. J. Neuroscience 18:2954-2961.
Letunic, I., L. Goodstadt, N. J. Dickens, J. Doerks, J. Schultz,R. Mott, F. Ciccarelli, R. R. Copley, C. P. Ponting & P. Bork. 2002. Recent improvements to the SMART domain based sequence annotation resource. Nucleic Acids Research 30: 242-244.
Liu, Y., D. M. Engelmann & M. Gerstein. 2002. Genomic analysis of membrane protein families: abundance and conserved motifs. Genome Biol. 3: research0054.
Mitaku, S., T. Hirokawa, & T. Tsuji. 2002. Amphiphilicity index of polar amino acids as an aid in the characterization of amino acid preference at membrane-water interfaces. Bioinformatics 18: 608-616.
McBain, C. J. & M. L. Mayer. 1994. N-Methyl-D-Aspartartic acid receptor structure and function. Physiol. Rev. 74: 723-760.
Moller, S., M. Croning, & R. Apweiler. 2001. Evaluation of methods for the prediction of membrane spanning regions. Bioinformatics 17:646-653.
Nakanishi, N., R. Axel, & N. A. Shneider. 1992. Alternative splicing generates functionally distinct N-methyl-D-aspartate receptors. Proc. Natl. Acad. Sci. USA, 89: 8552-8556.
Nusser, Z. 2000. AMPA and NMDA receptors, similarities and differences in their synaptic distribution. Curr. Opin. Neurobiol. 10: 337-341.
Paoletti, P., P. Ascher, & J. Neyton. 1997. High-affinity zinc inhibition of NMDA NR1-NR2A receptors. J. Neurosci. 17:5711-5725.
Raditsch, M., J. P. Ruppersberg, T. Kuner, W. Gunther, R. Schoepfer, P. H. Seeburg, W. Jahn & V. Witzemann. 1993. Subunit-specific block of cloned NMDA receptors by argiotoxin636. FEBS Lett. 324: 63-66.
Rao, J. K. M. & P. Argos. 1986. A conformational preference parameter to predict helices in integral membrane proteins. Biophys. Biochem. Acta, 869: 197-214.
Rosenmund, C., Y. Stern-Bach, & C. F. Stevens. 1998. The tetrameric structure of a glutamate receptor channel. Science 280: 1596-1599.
Rost, B. & C. Sander. 1994. Combinig evolutionary information and neural networks to predict protein secondary structure. Proteins 19:521-533.
Rost, B. 1996. PHD: predicting 1D protein structure by profile based neural networks. Meth. Enzymol. 266: 525-539.
Senes, A., M. Gerstein & D. M. Engelmann. 2000. Statistical analysis of amino acid patterns in transmembrane helices: The GxxxG motif occurs frequently and in association with b-branched residues at neighboring positions. J. Mol. Biol. 296:921-936.
Sprengel, R., B. Suchanek, C. Amico, R. Brusa, N. Burnashev, A. Rozov, O. Hvalby, V. Jensen, O. Paulsen, P. Andersen, J. J. Kim, R. F. Thompson, W. Sun, L. C. Webster, S. G. N. Grant, J. A. Eilers, J. Konnerth, Li, J. O. McNamara & P. H. Seeburg. 1998. Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo. Cell 92:279-289.
Traxler, B., D. Boyd, & J. Beckwith. 1993. The topological analysis of integral cytoplasmatic membrane proteins. J. Membrane Biol. 132: 1-11.
Tusnady, G. & I. Simon. 1998. Principles governing amino acid composition of integral membrane proteins: Application to topology prediction. J. Mol. Biol. 283: 489-506.
Tusnady, G. E. & I. Simon. 2001. The HMMTOP transmembrane topology prediction server. Bioinformatics 17: 849-850.
von Heijne, G. 1992. Membrane protein structure prediction. Hydrophobicity analysis and the positive inside rule. J. Mol. Biol. 225: 487-494.
Whitehorn, E. A., W. J. Dower, & M. Li. 1999. Expression of extracellular N-terminal domain of NMDA receptor in mammalian cells. In: Li, M.Ed. NMDA receptor protocols. Humana Press, Totowa, New Jersey. pp. 61-72.
Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-SinDerivadas 4.0.
Derechos de autor 2023 Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales