Toto Olivera: Conus Peptides

I. Venom Complexity
II. The Generation of Peptide Diversity
III. From Chemical Biology to Neuroscience

Part I: Venom Complexity

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iBiology Archives:Toto Olivera iBioSeminar (2006)

Lecture Overview
Although snails are not the first animals that come to mind when venoms are mentioned, there are, in fact, thousands of species of venomous predatory marine snails. The most intensively studied of these are the ~700 species of cone snails (Conus). Each snail species has ~100 different peptide neurotoxins present in its venom. Thus, conus venoms are a source of over 100,000 pharmacologically active peptides.  

In Part 1 of his lecture, Olivera tells us how he first became interested in studying conus venom. His lab found that conus venom peptides are organized into groups or “cabals” each of which act on a group of related molecular targets such as ion channels or receptors.  This venom complexity gives snails an advantage in capturing prey, resisting predators or repelling competitors.

As each species of snail evolved to fit a specific ecological niche, its venom also evolved to include different peptides.  In his second talk, Olivera explains that peptides are members of gene superfamilies.  Across a peptide family, some residues are highly conserved, while other residues are highly variable. Mutations in the variable regions allow the peptides to rapidly evolve to target different ion channels. Characterization of these peptides has led to the development of novel analgesic drugs.

In his final talk, Olivera describes how his lab has been using conotoxin peptides to decipher the vast complexity of K+ channel subtypes present in neurons. Recently, his lab began to characterize the venom of turrids, a tiny marine snail with over 12,000 species; these snails too have a complex mix of peptides neurotoxins.

Speaker Bio
Baldomero “Toto” Olivera received a B.S. degree in Chemistry from the University of the Philippines, a PhD in Biophysical Chemistry from Caltech and did his postdoctoral work at Stanford University. His early research contributions included the discovery and biochemical characterization of E. coli DNA ligase.

His laboratory initiated the identification and characterization of the biologically active peptides found in the venoms of predatory cone snails.  This led to a broad involvement with molecular neuroscience, particularly the functional role of ion channels and receptor subtypes in nervous systems. The Conus peptide project has raised wide ranging biological questions, from mechanisms of protein folding and post-translational modification, to gene organization and mechanisms of speciation; several Conus peptides discovered in Olivera's laboratory are being developed as therapeutics and one is approved as a commercial drug.

Olivera is currently a Distinguished Professor of Biology at the University of Utah and a Howard Hughes Medical Institute Professor. He is also a member of the National Academy of Sciences and the Institute of Medicine.

Related Talks

Related Articles

Olivera, B.M. (1997) E.E. Just Lecture - Conus venom peptides, receptor and ion channel targets, and drug design: 50 million years of neuropharmacology. Mol. Biol. Cell 8:2101-09.

Olivera, B.M. (2002) Conus venom peptides: reflections from the biology of clades and species. Annu. Rev. Ecol. Syst. 33:25-47.

Terlau H, Olivera BM. (2004) Conus venoms: a rich source of novel ion channel-targeted peptides.  Physiol Rev. 84(1):41-68. Review. PMID: 14715910

Advanced Reading:
Olivera, B.M., J. Rivier, C. Clark, C.A. Ramilo, G.P. Corpuz, F.C. Abogadie, E.E. Mena, S.R. Woodward, D.R. Hillyard and L.J. Cruz (1990) Diversity of Conus neuropeptides. Science 249:257-63.

Terlau, H., K. Shon, M. Grilley, M. Stocker, W. Stühmer and B.M. Olivera (1996) Strategy for rapid immobilization of prey by a fish-hunting cone snail. Nature 381:148-51. PMID: 12074021

Santos A.D., J.M. McIntosh, D.R. Hillyard, L.J. Cruz and B.M. Olivera (2004) The A-superfamily of conotoxins: structural and functional divergence. J. Biol. Chem. 279:17596-606.

Terlau, H. and B.M. Olivera (2004) Conus venoms: a rich source of novel ion channel-targeted peptides. Physiol. Rev. 83:41-68.

Teichert RW, Raghuraman S, Memon T, Cox JL, Foulkes T, Rivier JE, Olivera BM. (2012) Characterization of two neuronal subclasses through constellation pharmacology. Proc Natl Acad Sci U S A.109(31):12758-63. PMID: 22778416

Teichert RW, Memon T, Aman JW, Olivera BM. (2014) Using constellation pharmacology to define comprehensively a somatosensory neuronal subclass. Proc Natl Acad Sci U S A. 111(6):2319-24.PMID:24469798

Aman JW, Imperial JS, Ueberheide B, Zhang MM, Aguilar M, Taylor D, Watkins M, Yoshikami D, Showers-Corneli P, Safavi-Hemami H, Biggs J, Teichert RW, Olivera BM. (2015) Insights into the origins of fish hunting in venomous cone snails from studies of Conus tessulatus. Proc Natl Acad Sci U S A. 112(16):5087-92. PMID: 25848010

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