Definition of the M-Conotoxin Superfamily: Characterization of Novel Peptides from Molluscivorous Conus Venoms
| Autor: | Baldomero M. Olivera, James E. Garrett, Gloria P. Corpuz, Wenqin Li, J. Michael McIntosh, Owen M. McDougal, David R. Hillyard, Clark Colledge, Richard B. Jacobsen, Elsie C. Jimenez, William R. Gray, Lourdes J. Cruz, Craig S. Walker, Jean Rivier, Maren Watkins |
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| Rok vydání: | 2005 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization DNA Complementary Conus textile Molecular Sequence Data Peptide complex mixtures Biochemistry Mice Species Specificity Complementary DNA Conus Animals Amino Acid Sequence Disulfides Conotoxin Cloning Molecular Peptide sequence Injections Intraventricular chemistry.chemical_classification Behavior Animal biology biology.organism_classification Amino acid chemistry Multigene Family Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Conus Snail Conotoxins Peptides |
| Zdroj: | Biochemistry. 44:8176-8186 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi047541b |
| Popis: | Most of the50,000 different pharmacologically active peptides in Conus venoms belong to a small number of gene superfamilies. In this work, the M-conotoxin superfamily is defined using both biochemical and molecular criteria. Novel excitatory peptides purified from the venoms of the molluscivorous species Conus textile and Conus marmoreus all have a characteristic pattern of Cys residues previously found in the mu-, kappaM-, and psi-conotoxins (CC-C-C-CC). The new peptides are smaller (12-19 amino acids) than the mu-, kappaM-, and psi-conotoxins (22-24 amino acids). One peptide, mr3a, was chemically synthesized in a biologically active form. Analysis of the disulfide bridges of a natural peptide tx3c from C. textile and synthetic peptide mr3a from C. marmoreus showed a novel pattern of disulfide connectivity, different from that previously established for the mu- and psi-conotoxins. Thus, these peptides belong to a new group of structurally and pharmacologically distinct conotoxins that are particularly prominent in the venoms of mollusc-hunting Conus species. Analysis of cDNA clones encoding the novel peptides as well as those encoding mu-, kappaM-, and psi-conotoxins revealed highly conserved amino acid residues in the precursor sequences; this conservation in both amino acid sequence and in the Cys pattern defines a gene superfamily, designated the M-conotoxin superfamily. The peptides characterized can be provisionally assigned to four distinct groups within the M-superfamily based on sequence similarity within and divergence between each group. A notable feature of the superfamily is that two distinct structural frameworks have been generated by changing the disulfide connectivity on an otherwise conserved Cys pattern. |
| Databáze: | OpenAIRE |
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