For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
16
views
51
references
 Top references
cited by
7
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      454
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Scorpion Toxin Tf2 from Tityus fasciolatus Promotes Na v1.3 Opening

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          We identified Tf2, the first β-scorpion toxin from the venom of the Brazilian scorpion Tityus fasciolatus. Tf2 is identical to Tb2-II found in Tityus bahiensis. We found that Tf2 selectively activates human (h)Na v1.3, a neuronal voltage-gated sodium (Na v) subtype implicated in epilepsy and nociception. Tf2 shifts hNa v1.3 activation voltage to more negative values, thereby opening the channel at resting membrane potentials. Seven other tested mammalian Na v channels (Na v1.1-1.2; Na v1.4-1.8) expressed in Xenopus oocytes are insensitive upon application of 1 μM Tf2. Therefore, the identification of Tf2 represents a unique addition to the repertoire of animal toxins that can be used to investigate Na v channel function.

          Related collections

          Most cited references51

          • Record: found
          • Abstract: found
          • Article: not found

          Protein homology detection by HMM-HMM comparison.

          Johannes Söding (2005)
          Protein homology detection and sequence alignment are at the basis of protein structure prediction, function prediction and evolution. We have generalized the alignment of protein sequences with a profile hidden Markov model (HMM) to the case of pairwise alignment of profile HMMs. We present a method for detecting distant homologous relationships between proteins based on this approach. The method (HHsearch) is benchmarked together with BLAST, PSI-BLAST, HMMER and the profile-profile comparison tools PROF_SIM and COMPASS, in an all-against-all comparison of a database of 3691 protein domains from SCOP 1.63 with pairwise sequence identities below 20%.Sensitivity: When the predicted secondary structure is included in the HMMs, HHsearch is able to detect between 2.7 and 4.2 times more homologs than PSI-BLAST or HMMER and between 1.44 and 1.9 times more than COMPASS or PROF_SIM for a rate of false positives of 10%. Approximately half of the improvement over the profile-profile comparison methods is attributable to the use of profile HMMs in place of simple profiles. Alignment quality: Higher sensitivity is mirrored by an increased alignment quality. HHsearch produced 1.2, 1.7 and 3.3 times more good alignments ('balanced' score >0.3) than the next best method (COMPASS), and 1.6, 2.9 and 9.4 times more than PSI-BLAST, at the family, superfamily and fold level, respectively.Speed: HHsearch scans a query of 200 residues against 3691 domains in 33 s on an AMD64 2GHz PC. This is 10 times faster than PROF_SIM and 17 times faster than COMPASS.
          Article 0 comments Cited 961 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Tracking Voltage-dependent Conformational Changes in Skeletal Muscle Sodium Channel during Activation

            Baron Chanda, Francisco Bezanilla (2002)
            The primary voltage sensor of the sodium channel is comprised of four positively charged S4 segments that mainly differ in the number of charged residues and are expected to contribute differentially to the gating process. To understand their kinetic and steady-state behavior, the fluorescence signals from the sites proximal to each of the four S4 segments of a rat skeletal muscle sodium channel were monitored simultaneously with either gating or ionic currents. At least one of the kinetic components of fluorescence from every S4 segment correlates with movement of gating charge. The fast kinetic component of fluorescence from sites S216C (S4 domain I), S660C (S4 domain II), and L1115C (S4 domain III) is comparable to the fast component of gating currents. In contrast, the fast component of fluorescence from the site S1436C (S4 domain IV) correlates with the slow component of gating. In all the cases, the slow component of fluorescence does not have any apparent correlation with charge movement. The fluorescence signals from sites reflecting the movement of S4s in the first three domains initiate simultaneously, whereas the fluorescence signals from the site S1436C exhibit a lag phase. These results suggest that the voltage-dependent movement of S4 domain IV is a later step in the activation sequence. Analysis of equilibrium and kinetic properties of fluorescence over activation voltage range indicate that S4 domain III is likely to move at most hyperpolarized potentials, whereas the S4s in domain I and domain II move at more depolarized potentials. The kinetics of fluorescence changes from sites near S4-DIV are slower than the activation time constants, suggesting that the voltage-dependent movement of S4-DIV may not be a prerequisite for channel opening. These experiments allow us to map structural features onto the kinetic landscape of a sodium channel during activation.
            Article 0 comments Cited 110 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Deconstructing voltage sensor function and pharmacology in sodium channels

              Frank Bosmans, Marie Martin-Eauclaire, Kenton J. Swartz (2008)
              Voltage-activated sodium (Nav) channels are crucial for the generation and propagation of nerve impulses, and as such are amongst the most widely targeted ion channels by toxins and drugs. The four voltage sensors in Nav channels have distinct amino acid sequences, raising fundamental questions about their relative contributions to the function and pharmacology of the channel. Here we use four-fold symmetric voltage-activated potassium (Kv) channels as reporters to examine the contributions of individual Nav channel S3b-S4 paddle motifs to the kinetics of voltage sensor activation and to forming toxin receptors. Our results uncover binding sites for toxins from tarantula and scorpion venom on each of the four paddle motifs in Nav channels and reveal how paddle-specific interactions can be used to reshape Nav channel activity. One paddle motif is unique in that it slows voltage sensor activation and toxins selectively targeting this motif impede Nav channel inactivation. This reporter approach and the principles that emerge will be useful in developing new drugs for treating pain and Nav channelopathies.
              Article 0 comments Cited 96 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Alexander Binshtok: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 17 June 2015
                Publication date Collection: 2015
                Volume: 10
                Issue: 6
                Electronic Location Identifier: e0128578
                Affiliations
                [1 ]Departamento de Ciências Fisiológicas, Laboratório de Toxinologia, Universidade de Brasília, Brasília, DF, Brazil
                [2 ]Department of Physiology, Johns Hopkins University—School of Medicine, Baltimore, MD, United States of America
                [3 ]Solomon H. Snyder Department of Neuroscience, Johns Hopkins University—School of Medicine, Baltimore, MD, United States of America
                The Hebrew University Medical School, ISRAEL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: TSC FB EFS. Performed the experiments: TSC FB CBFM SCR. Analyzed the data: TSC FB CBFM SCR EFS. Contributed reagents/materials/analysis tools: FB EFS. Wrote the paper: TSC FB CBFM SCR EFS.

                Article
                Publisher ID: PONE-D-14-39052
                DOI: 10.1371/journal.pone.0128578
                PMC ID: 4470819
                PubMed ID: 26083731
                SO-VID: 93dceec0-bede-4ed6-80cd-25c844a29550
                Copyright statement: Copyright @ 2015
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                Date received : 30 August 2014
                Date accepted : 29 April 2015
                Page count
                Figures: 5, Tables: 0, Pages: 14
                Funding
                Parts of the research in this publication were supported by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) under award number R00NS073797 (F.B.) and by CNPq (564.223/2010-7)/FAPDF (193.000.471/2011) (INOVATOXIN project) (E.F.S). T.S.C. is a graduate student financed by CNPq and CAPES Foundation. S.C.R. and C.B.F.M. are graduate students supported by CNPq. E.F.S. receives support from CNPq. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Custom metadata
                Data Availability All relevant data are within the paper.

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

                Comments

                Comment on this article

                scite_

                Similar content454

                See all similar

                Cited by6

                See all cited by

                Most referenced authors1,408

                See all reference authors