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Your search keyword '"Yanni K Y, Chin"' showing total 2 results
Start Over Author "Yanni K Y, Chin" Journal scientific reports
2 results on '"Yanni K Y, Chin"'

1. The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity

Author

Joshua S. Wingerd, Christine A. Mozar, Christine A. Ussing, Swetha S. Murali, Yanni K.-Y. Chin, Ben Cristofori-Armstrong, Thomas Durek, John Gilchrist, Christopher W. Vaughan, Frank Bosmans, David J. Adams, Richard J. Lewis, Paul F. Alewood, Mehdi Mobli, Macdonald J. Christie, and Lachlan D. Rash

Subjects
Medicine, Science
Abstract

Abstract Voltage-gated sodium (NaV) channels are essential for the transmission of pain signals in humans making them prime targets for the development of new analgesics. Spider venoms are a rich source of peptide modulators useful to study ion channel structure and function. Here we describe β/δ-TRTX-Pre1a, a 35-residue tarantula peptide that selectively interacts with neuronal NaV channels inhibiting peak current of hNaV1.1, rNaV1.2, hNaV1.6, and hNaV1.7 while concurrently inhibiting fast inactivation of hNaV1.1 and rNaV1.3. The DII and DIV S3-S4 loops of NaV channel voltage sensors are important for the interaction of Pre1a with NaV channels but cannot account for its unique subtype selectivity. Through analysis of the binding regions we ascertained that the variability of the S1-S2 loops between NaV channels contributes substantially to the selectivity profile observed for Pre1a, particularly with regards to fast inactivation. A serine residue on the DIV S2 helix was found to be sufficient to explain Pre1a’s potent and selective inhibitory effect on the fast inactivation process of NaV1.1 and 1.3. This work highlights that interactions with both S1-S2 and S3-S4 of NaV channels may be necessary for functional modulation, and that targeting the diverse S1-S2 region within voltage-sensing domains provides an avenue to develop subtype selective tools.

Published
2017
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2. The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity

Author

Paul F. Alewood, Thomas Durek, Ben Cristofori-Armstrong, Swetha S. Murali, David J. Adams, Yanni K.-Y. Chin, Lachlan D. Rash, Richard J. Lewis, Christine A. Ussing, Joshua S. Wingerd, Frank Bosmans, Christine A. Mozar, MacDonald J. Christie, Christopher W. Vaughan, Mehdi Mobli, and John Gilchrist

Subjects
Models, Molecular, 0301 basic medicine, Science, Spider Venoms, Peptide, Voltage-Gated Sodium Channels, Plasma protein binding, Article, Protein Structure, Secondary, Serine, 03 medical and health sciences, Animals, Humans, Binding site, Ion channel, chemistry.chemical_classification, Binding Sites, Multidisciplinary, Sodium channel, HEK 293 cells, Spiders, 3. Good health, HEK293 Cells, 030104 developmental biology, Gene Expression Regulation, chemistry, Biophysics, Medicine, Peptides, Selectivity, Protein Binding
Abstract

Voltage-gated sodium (NaV) channels are essential for the transmission of pain signals in humans making them prime targets for the development of new analgesics. Spider venoms are a rich source of peptide modulators useful to study ion channel structure and function. Here we describe β/δ-TRTX-Pre1a, a 35-residue tarantula peptide that selectively interacts with neuronal NaV channels inhibiting peak current of hNaV1.1, rNaV1.2, hNaV1.6, and hNaV1.7 while concurrently inhibiting fast inactivation of hNaV1.1 and rNaV1.3. The DII and DIV S3-S4 loops of NaV channel voltage sensors are important for the interaction of Pre1a with NaV channels but cannot account for its unique subtype selectivity. Through analysis of the binding regions we ascertained that the variability of the S1-S2 loops between NaV channels contributes substantially to the selectivity profile observed for Pre1a, particularly with regards to fast inactivation. A serine residue on the DIV S2 helix was found to be sufficient to explain Pre1a’s potent and selective inhibitory effect on the fast inactivation process of NaV1.1 and 1.3. This work highlights that interactions with both S1-S2 and S3-S4 of NaV channels may be necessary for functional modulation, and that targeting the diverse S1-S2 region within voltage-sensing domains provides an avenue to develop subtype selective tools.

Published
2017

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