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http://purl.uniprot.org/citations/23703613http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23703613http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23703613http://www.w3.org/2000/01/rdf-schema#comment"In the present study, we investigated the structure and function of hainantoxin-III (HNTX-III), a 33-residue polypeptide from the venom of the spider Ornithoctonus hainana. It is a selective antagonist of neuronal tetrodotoxin-sensitive voltage-gated sodium channels. HNTX-III suppressed Nav1.7 current amplitude without significantly altering the activation, inactivation, and repriming kinetics. Short extreme depolarizations partially activated the toxin-bound channel, indicating voltage-dependent inhibition of HNTX-III. HNTX-III increased the deactivation of the Nav1.7 current after extreme depolarizations. The HNTX-III·Nav1.7 complex was gradually dissociated upon prolonged strong depolarizations in a voltage-dependent manner, and the unbound toxin rebound to Nav1.7 after a long repolarization. Moreover, analysis of chimeric channels showed that the DIIS3-S4 linker was critical for HNTX-III binding to Nav1.7. These data are consistent with HNTX-III interacting with Nav1.7 site 4 and trapping the domain II voltage sensor in the closed state. The solution structure of HNTX-III was determined by two-dimensional NMR and shown to possess an inhibitor cystine knot motif. Structural analysis indicated that certain basic, hydrophobic, and aromatic residues mainly localized in the C terminus may constitute an amphiphilic surface potentially involved in HNTX-III binding to Nav1.7. Taken together, our results show that HNTX-III is distinct from β-scorpion toxins and other β-spider toxins in its mechanism of action and binding specificity and affinity. The present findings contribute to our understanding of the mechanism of toxin-sodium channel interaction and provide a useful tool for the investigation of the structure and function of sodium channel isoforms and for the development of analgesics."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m112.426627"xsd:string
http://purl.uniprot.org/citations/23703613http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m112.426627"xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Cai T."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Cai T."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Deng M."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Deng M."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Hu W."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Hu W."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Liu Y."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Liu Y."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Li J."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Li J."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Liu Z."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Liu Z."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Li D."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Li D."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Li J.'"xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Li J.'"xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Liang S."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Liang S."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Zhou X."xsd:string
http://purl.uniprot.org/citations/23703613http://purl.uniprot.org/core/author"Zhou X."xsd:string