In:
PLOS Biology, Public Library of Science (PLoS), Vol. 21, No. 8 ( 2023-8-3), p. e3002217-
Abstract:
Animal venom peptides represent valuable compounds for biomedical exploration. The venoms of marine cone snails constitute a particularly rich source of peptide toxins, known as conotoxins. Here, we identify the sequence of an unusually large conotoxin, Mu8.1, which defines a new class of conotoxins evolutionarily related to the well-known con-ikot-ikots and 2 additional conotoxin classes not previously described. The crystal structure of recombinant Mu8.1 displays a saposin-like fold and shows structural similarity with con-ikot-ikot. Functional studies demonstrate that Mu8.1 curtails calcium influx in defined classes of murine somatosensory dorsal root ganglion (DRG) neurons. When tested on a variety of recombinantly expressed voltage-gated ion channels, Mu8.1 displayed the highest potency against the R-type (Cav2.3) calcium channel. Ca 2+ signals from Mu8.1-sensitive DRG neurons were also inhibited by SNX-482, a known spider peptide modulator of Cav2.3 and voltage-gated K + (Kv4) channels. Our findings highlight the potential of Mu8.1 as a molecular tool to identify and study neuronal subclasses expressing Cav2.3. Importantly, this multidisciplinary study showcases the potential of uncovering novel structures and bioactivities within the largely unexplored group of macro-conotoxins.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3002217
DOI:
10.1371/journal.pbio.3002217.g001
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10.1371/journal.pbio.3002217.g002
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10.1371/journal.pbio.3002217.g003
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10.1371/journal.pbio.3002217.g004
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10.1371/journal.pbio.3002217.g005
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10.1371/journal.pbio.3002217.g006
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10.1371/journal.pbio.3002217.g007
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10.1371/journal.pbio.3002217.t001
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10.1371/journal.pbio.3002217.s001
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10.1371/journal.pbio.3002217.s002
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10.1371/journal.pbio.3002217.s003
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10.1371/journal.pbio.3002217.s004
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10.1371/journal.pbio.3002217.s005
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10.1371/journal.pbio.3002217.s006
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10.1371/journal.pbio.3002217.s007
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10.1371/journal.pbio.3002217.s008
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10.1371/journal.pbio.3002217.s009
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10.1371/journal.pbio.3002217.s010
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10.1371/journal.pbio.3002217.s011
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10.1371/journal.pbio.3002217.s012
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10.1371/journal.pbio.3002217.s013
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10.1371/journal.pbio.3002217.s014
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10.1371/journal.pbio.3002217.s015
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10.1371/journal.pbio.3002217.s016
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10.1371/journal.pbio.3002217.s017
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10.1371/journal.pbio.3002217.s018
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10.1371/journal.pbio.3002217.s019
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10.1371/journal.pbio.3002217.s020
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10.1371/journal.pbio.3002217.s021
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10.1371/journal.pbio.3002217.s022
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10.1371/journal.pbio.3002217.s023
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10.1371/journal.pbio.3002217.s024
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10.1371/journal.pbio.3002217.s029
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10.1371/journal.pbio.3002217.s030
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10.1371/journal.pbio.3002217.s031
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10.1371/journal.pbio.3002217.s032
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10.1371/journal.pbio.3002217.r001
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10.1371/journal.pbio.3002217.r002
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10.1371/journal.pbio.3002217.r003
DOI:
10.1371/journal.pbio.3002217.r004
DOI:
10.1371/journal.pbio.3002217.r005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2126773-X
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