Chemical Communication in a Post-Genomic World (2003) / Chapter Skim
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11 Efficient oxidative folding of conotoxins and the radiation of venomous cone snails
11 Efficient oxidative folding of conotoxins and the radiation of venomous cone snails
Pages 50-56
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From page 50... ...
2 The analysis carried out on Conus venom peptides suggests that a majority of the estimated >SO,OOO peptides are encoded by only ~12 conotoxin gene superfamilies. These superfamilies have undergone rapid amplification and divergence, accompanying the parallel radiation and diversification of Conus species at a macroevolutionary level (~Conus is arguably the most speciesrich genus of living marine invertebrates)
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From page 51... ...
For potential intermolecular interactions, we show that multiple isoforms of protein disulfide isomerase (PDI) , which catalyze protein thiol disulfide exchange reactions, are present within Conus venom ducts, and we show that, apart from the conotoxins themselves, these isoforms are the major soluble protein components of the ducts.
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From page 52... ...
Results PDI Is the Major Soluble High Molecular Weight Polypeptidic Component of Conus Venom Ducts. The oxidative folding of secreted proteins with disulfide bonds is thought to be promoted by PDIs (7, 8~.
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From page 53... ...
is shown, and a comparison of the sequences of four Gla-containing Conus venom peptides to the N-terminal sequence of human blood clotting factor IX is shown. Note that one Conus oentide, conantokin-G from C qeooranhus, has a Gla domain motif that has similar soac~na to factor IX (see boxed seouences)
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From page 54... ...
. Discussion In the course of their evolutionary history, the venomous cone snails have developed an unprecedented number of diverse, highly structured peptides that are expressed in their venom ducts.
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From page 55... ...
The striking contrast found between the conserved signal sequence and propeptide regions versus the hypermutable mature toxin region led to the suggestion that the conserved regions of the precursor were essential for proper folding "such that the single biologically active disulfide-bonded configuration can be specifically formed." It was pointed out in the same paper that in vivo, additional factors to facilitate the folding process might be required, such as PDI; in this work, we provided the characterization of PDI from Conus venom ducts. Evidence that posttranslational modification enzymes may also be extrinsic factors that facilitate proper folding was presented above.
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From page 56... ...
As we understand more about the oxidative folding process, we should in principle be able to determine at which point the various components that facilitate oxidative folding of conotoxins appear. Thus, one question that can be evaluated through a comparison of different early diverging lineages is whether most of these adaptations took place early in the history of the genus, or whether a breakthrough in folding smaller conotoxins could have been a factor that made the major radiation of cone snails in the Miocene possible.
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