Central loop of non-conventional toxin WTX from Naja kaouthia is important for interaction with nicotinic acetylcholine receptors
‘Three-finger’ toxin WTX from Naja kaouthia interacts with nicotinic and muscarinic acetylcholine receptors (nAChRs and mAChRs). Mutagenesis and competition experiments with 125I-α-bungarotoxin revealed that Arg31 and Arg32 residues from the WTX loop II are important for binding to Torpedo californi...
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| Veröffentlicht in: | Toxicon (Oxford) 2016-09, Vol.119, p.274-279 |
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| creator | Lyukmanova, Ekaterina N. Shulepko, Mikhail A. Shenkarev, Zakhar O. Kasheverov, Igor E. Chugunov, Anton O. Kulbatskii, Dmitrii S. Myshkin, Mikhail Yu Utkin, Yuri N. Efremov, Roman G. Tsetlin, Victor I. Arseniev, Alexander S. Kirpichnikov, Mikhail P. Dolgikh, Dmitry A. |
| description | ‘Three-finger’ toxin WTX from Naja kaouthia interacts with nicotinic and muscarinic acetylcholine receptors (nAChRs and mAChRs). Mutagenesis and competition experiments with 125I-α-bungarotoxin revealed that Arg31 and Arg32 residues from the WTX loop II are important for binding to Torpedo californica and human α7 nAChRs. Computer modeling suggested that loop II occupies the orthosteric binding site at α7 nAChR. The similar toxin interface was previously described as a major determinant of allosteric interactions with mAChRs.
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•Mutagenesis of non-conventional toxin WTX from Naja kaouthia is performed.•Activity of WTX and its mutants on muscle-type and α7-type of nAChRs was studied.•R31 and R32 from the loop II is important for binding to both types of receptors.•Modeling revealed the loop II entering into the orthosteric site of the α7 nAChRs. |
| doi_str_mv | 10.1016/j.toxicon.2016.06.012 |
| format | Article |
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[Display omitted]
•Mutagenesis of non-conventional toxin WTX from Naja kaouthia is performed.•Activity of WTX and its mutants on muscle-type and α7-type of nAChRs was studied.•R31 and R32 from the loop II is important for binding to both types of receptors.•Modeling revealed the loop II entering into the orthosteric site of the α7 nAChRs.</description><identifier>ISSN: 0041-0101</identifier><identifier>EISSN: 1879-3150</identifier><identifier>DOI: 10.1016/j.toxicon.2016.06.012</identifier><identifier>PMID: 27343701</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Amino Acid Sequence ; Binding ; Binding sites ; Computer modeling ; Computer simulation ; Determinants ; Elapid Venoms - chemistry ; Elapid Venoms - genetics ; Elapid Venoms - toxicity ; Humans ; Ly-6/uPAR ; Mathematical models ; Mutagenesis, Site-Directed ; Naja kaouthia ; Nicotinic acetylcholine receptor ; Receptors ; Receptors, Nicotinic - drug effects ; Residues ; Sequence Homology, Amino Acid ; Site-directed mutagenesis ; Snake neurotoxin ; Three-finger protein ; Torpedo californica ; Toxins</subject><ispartof>Toxicon (Oxford), 2016-09, Vol.119, p.274-279</ispartof><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c431t-7d29567431c2cccaba5f9615e4bc3c7cd960bb4c9aaa6a66fee9af0525e399943</citedby><cites>FETCH-LOGICAL-c431t-7d29567431c2cccaba5f9615e4bc3c7cd960bb4c9aaa6a66fee9af0525e399943</cites><orcidid>0000-0002-4609-970X ; 0000-0003-1331-3949</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.toxicon.2016.06.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,782,786,3552,27931,27932,46002</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27343701$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lyukmanova, Ekaterina N.</creatorcontrib><creatorcontrib>Shulepko, Mikhail A.</creatorcontrib><creatorcontrib>Shenkarev, Zakhar O.</creatorcontrib><creatorcontrib>Kasheverov, Igor E.</creatorcontrib><creatorcontrib>Chugunov, Anton O.</creatorcontrib><creatorcontrib>Kulbatskii, Dmitrii S.</creatorcontrib><creatorcontrib>Myshkin, Mikhail Yu</creatorcontrib><creatorcontrib>Utkin, Yuri N.</creatorcontrib><creatorcontrib>Efremov, Roman G.</creatorcontrib><creatorcontrib>Tsetlin, Victor I.</creatorcontrib><creatorcontrib>Arseniev, Alexander S.</creatorcontrib><creatorcontrib>Kirpichnikov, Mikhail P.</creatorcontrib><creatorcontrib>Dolgikh, Dmitry A.</creatorcontrib><title>Central loop of non-conventional toxin WTX from Naja kaouthia is important for interaction with nicotinic acetylcholine receptors</title><title>Toxicon (Oxford)</title><addtitle>Toxicon</addtitle><description>‘Three-finger’ toxin WTX from Naja kaouthia interacts with nicotinic and muscarinic acetylcholine receptors (nAChRs and mAChRs). Mutagenesis and competition experiments with 125I-α-bungarotoxin revealed that Arg31 and Arg32 residues from the WTX loop II are important for binding to Torpedo californica and human α7 nAChRs. Computer modeling suggested that loop II occupies the orthosteric binding site at α7 nAChR. The similar toxin interface was previously described as a major determinant of allosteric interactions with mAChRs.
[Display omitted]
•Mutagenesis of non-conventional toxin WTX from Naja kaouthia is performed.•Activity of WTX and its mutants on muscle-type and α7-type of nAChRs was studied.•R31 and R32 from the loop II is important for binding to both types of receptors.•Modeling revealed the loop II entering into the orthosteric site of the α7 nAChRs.</description><subject>Amino Acid Sequence</subject><subject>Binding</subject><subject>Binding sites</subject><subject>Computer modeling</subject><subject>Computer simulation</subject><subject>Determinants</subject><subject>Elapid Venoms - chemistry</subject><subject>Elapid Venoms - genetics</subject><subject>Elapid Venoms - toxicity</subject><subject>Humans</subject><subject>Ly-6/uPAR</subject><subject>Mathematical models</subject><subject>Mutagenesis, Site-Directed</subject><subject>Naja kaouthia</subject><subject>Nicotinic acetylcholine receptor</subject><subject>Receptors</subject><subject>Receptors, Nicotinic - drug effects</subject><subject>Residues</subject><subject>Sequence Homology, Amino Acid</subject><subject>Site-directed mutagenesis</subject><subject>Snake neurotoxin</subject><subject>Three-finger protein</subject><subject>Torpedo californica</subject><subject>Toxins</subject><issn>0041-0101</issn><issn>1879-3150</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUU1v3CAURFWrZpP2J7Ti2Is3YAxeTlW1ykelqL2kam_oGT9r2drgAJsmx_7zsNpNrq30BA-YeYNmCPnA2ZIzrs63yxwenA1-WZfjkpXi9Suy4KtWV4JL9posGGt4xQr8hJymtGWMiZVWb8lJ3YpGtIwvyN81-hxhpGMIMw0D9cFXZep9uXbBl4e9jKc_b3_RIYaJfoMt0N8QdnnjgLpE3TSHmMFnOoRInc8Ywe659I_LG-rLH7MrKwWL-XG0mzA6jzSixTmHmN6RNwOMCd8f9zPy4_Lidn1d3Xy_-rr-clPZRvBctX2tpWpLb2trLXQgB624xKazwra214p1XWM1AChQakDUMDBZSxRa60ackU-HuXMMdztM2UwuWRxH8Bh2yfCVkKpppBT_AeXFZsVaWaDyALUxpBRxMHN0E8RHw5nZB2W25hiU2QdlWCleF97Ho8Sum7B_YT0nUwCfDwAsntw7jCZZh95i74p12fTB_UPiCaw6qlI</recordid><startdate>20160901</startdate><enddate>20160901</enddate><creator>Lyukmanova, Ekaterina N.</creator><creator>Shulepko, Mikhail A.</creator><creator>Shenkarev, Zakhar O.</creator><creator>Kasheverov, Igor E.</creator><creator>Chugunov, Anton O.</creator><creator>Kulbatskii, Dmitrii S.</creator><creator>Myshkin, Mikhail Yu</creator><creator>Utkin, Yuri N.</creator><creator>Efremov, Roman G.</creator><creator>Tsetlin, Victor I.</creator><creator>Arseniev, Alexander S.</creator><creator>Kirpichnikov, Mikhail P.</creator><creator>Dolgikh, Dmitry A.</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>8FD</scope><scope>FR3</scope><scope>KR7</scope><orcidid>https://orcid.org/0000-0002-4609-970X</orcidid><orcidid>https://orcid.org/0000-0003-1331-3949</orcidid></search><sort><creationdate>20160901</creationdate><title>Central loop of non-conventional toxin WTX from Naja kaouthia is important for interaction with nicotinic acetylcholine receptors</title><author>Lyukmanova, Ekaterina N. ; Shulepko, Mikhail A. ; Shenkarev, Zakhar O. ; Kasheverov, Igor E. ; Chugunov, Anton O. ; Kulbatskii, Dmitrii S. ; Myshkin, Mikhail Yu ; Utkin, Yuri N. ; Efremov, Roman G. ; Tsetlin, Victor I. ; Arseniev, Alexander S. ; Kirpichnikov, Mikhail P. ; Dolgikh, Dmitry A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c431t-7d29567431c2cccaba5f9615e4bc3c7cd960bb4c9aaa6a66fee9af0525e399943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Amino Acid Sequence</topic><topic>Binding</topic><topic>Binding sites</topic><topic>Computer modeling</topic><topic>Computer simulation</topic><topic>Determinants</topic><topic>Elapid Venoms - chemistry</topic><topic>Elapid Venoms - genetics</topic><topic>Elapid Venoms - toxicity</topic><topic>Humans</topic><topic>Ly-6/uPAR</topic><topic>Mathematical models</topic><topic>Mutagenesis, Site-Directed</topic><topic>Naja kaouthia</topic><topic>Nicotinic acetylcholine receptor</topic><topic>Receptors</topic><topic>Receptors, Nicotinic - drug effects</topic><topic>Residues</topic><topic>Sequence Homology, Amino Acid</topic><topic>Site-directed mutagenesis</topic><topic>Snake neurotoxin</topic><topic>Three-finger protein</topic><topic>Torpedo californica</topic><topic>Toxins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lyukmanova, Ekaterina N.</creatorcontrib><creatorcontrib>Shulepko, Mikhail A.</creatorcontrib><creatorcontrib>Shenkarev, Zakhar O.</creatorcontrib><creatorcontrib>Kasheverov, Igor E.</creatorcontrib><creatorcontrib>Chugunov, Anton O.</creatorcontrib><creatorcontrib>Kulbatskii, Dmitrii S.</creatorcontrib><creatorcontrib>Myshkin, Mikhail Yu</creatorcontrib><creatorcontrib>Utkin, Yuri N.</creatorcontrib><creatorcontrib>Efremov, Roman G.</creatorcontrib><creatorcontrib>Tsetlin, Victor I.</creatorcontrib><creatorcontrib>Arseniev, Alexander S.</creatorcontrib><creatorcontrib>Kirpichnikov, Mikhail P.</creatorcontrib><creatorcontrib>Dolgikh, Dmitry A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Civil Engineering Abstracts</collection><jtitle>Toxicon (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lyukmanova, Ekaterina N.</au><au>Shulepko, Mikhail A.</au><au>Shenkarev, Zakhar O.</au><au>Kasheverov, Igor E.</au><au>Chugunov, Anton O.</au><au>Kulbatskii, Dmitrii S.</au><au>Myshkin, Mikhail Yu</au><au>Utkin, Yuri N.</au><au>Efremov, Roman G.</au><au>Tsetlin, Victor I.</au><au>Arseniev, Alexander S.</au><au>Kirpichnikov, Mikhail P.</au><au>Dolgikh, Dmitry A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Central loop of non-conventional toxin WTX from Naja kaouthia is important for interaction with nicotinic acetylcholine receptors</atitle><jtitle>Toxicon (Oxford)</jtitle><addtitle>Toxicon</addtitle><date>2016-09-01</date><risdate>2016</risdate><volume>119</volume><spage>274</spage><epage>279</epage><pages>274-279</pages><issn>0041-0101</issn><eissn>1879-3150</eissn><abstract>‘Three-finger’ toxin WTX from Naja kaouthia interacts with nicotinic and muscarinic acetylcholine receptors (nAChRs and mAChRs). Mutagenesis and competition experiments with 125I-α-bungarotoxin revealed that Arg31 and Arg32 residues from the WTX loop II are important for binding to Torpedo californica and human α7 nAChRs. Computer modeling suggested that loop II occupies the orthosteric binding site at α7 nAChR. The similar toxin interface was previously described as a major determinant of allosteric interactions with mAChRs.
[Display omitted]
•Mutagenesis of non-conventional toxin WTX from Naja kaouthia is performed.•Activity of WTX and its mutants on muscle-type and α7-type of nAChRs was studied.•R31 and R32 from the loop II is important for binding to both types of receptors.•Modeling revealed the loop II entering into the orthosteric site of the α7 nAChRs.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27343701</pmid><doi>10.1016/j.toxicon.2016.06.012</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-4609-970X</orcidid><orcidid>https://orcid.org/0000-0003-1331-3949</orcidid></addata></record> |
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| ispartof | Toxicon (Oxford), 2016-09, Vol.119, p.274-279 |
| issn | 0041-0101 1879-3150 |
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| subjects | Amino Acid Sequence Binding Binding sites Computer modeling Computer simulation Determinants Elapid Venoms - chemistry Elapid Venoms - genetics Elapid Venoms - toxicity Humans Ly-6/uPAR Mathematical models Mutagenesis, Site-Directed Naja kaouthia Nicotinic acetylcholine receptor Receptors Receptors, Nicotinic - drug effects Residues Sequence Homology, Amino Acid Site-directed mutagenesis Snake neurotoxin Three-finger protein Torpedo californica Toxins |
| title | Central loop of non-conventional toxin WTX from Naja kaouthia is important for interaction with nicotinic acetylcholine receptors |
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