An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding
Substitution of a cysteine in the extracellular mouth of the pore of the Shaker-delta K+ channel permits allosteric inhibition of the channel by Zn2+ or Cd2+ ions at micromolar concentrations. Cd2+ binds weakly to the open state but drives the channel into the slow (C-type) inactivated state, which...
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| Veröffentlicht in: | Biophysical journal 1994-04, Vol.66 (4), p.1068-1075 |
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| container_title | Biophysical journal |
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| creator | Yellen, G. Sodickson, D. Chen, T.Y. Jurman, M.E. |
| description | Substitution of a cysteine in the extracellular mouth of the pore of the Shaker-delta K+ channel permits allosteric inhibition of the channel by Zn2+ or Cd2+ ions at micromolar concentrations. Cd2+ binds weakly to the open state but drives the channel into the slow (C-type) inactivated state, which has a Kd for Cd2+ of approximately 0.2 microM. There is a 45,000-fold increase in affinity when the channel changes from open to inactivated. These results indicate that C-type inactivation involves a structural change in the external mouth of the pore. This structural change is reflected in the T449C mutant as state-dependent metal affinity, which may result either from a change in proximity of the introduced cysteine residues of the four subunits or from a change of the exposure of this residue on the surface of the protein. |
| doi_str_mv | 10.1016/S0006-3495(94)80888-4 |
| format | Article |
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Cd2+ binds weakly to the open state but drives the channel into the slow (C-type) inactivated state, which has a Kd for Cd2+ of approximately 0.2 microM. There is a 45,000-fold increase in affinity when the channel changes from open to inactivated. These results indicate that C-type inactivation involves a structural change in the external mouth of the pore. This structural change is reflected in the T449C mutant as state-dependent metal affinity, which may result either from a change in proximity of the introduced cysteine residues of the four subunits or from a change of the exposure of this residue on the surface of the protein.</description><identifier>ISSN: 0006-3495</identifier><identifier>EISSN: 1542-0086</identifier><identifier>DOI: 10.1016/S0006-3495(94)80888-4</identifier><identifier>PMID: 8038379</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Allosteric Regulation - genetics ; Animals ; Binding Sites ; Biophysical Phenomena ; Biophysics ; Cadmium - metabolism ; Cadmium - pharmacology ; Cell Line ; Cysteine - genetics ; Cysteine - metabolism ; Humans ; Kinetics ; Models, Biological ; Mutagenesis, Site-Directed ; Potassium Channel Blockers ; Potassium Channels - genetics ; Potassium Channels - metabolism ; Protein Binding ; Protein Conformation ; Protein Engineering ; Zinc - metabolism</subject><ispartof>Biophysical journal, 1994-04, Vol.66 (4), p.1068-1075</ispartof><rights>1994 The Biophysical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-bfe70364a50ba31785be84f74a634c87db2986861530ae448fb14b00b46bd7203</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1275814/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006349594808884$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,3537,27901,27902,53766,53768,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8038379$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yellen, G.</creatorcontrib><creatorcontrib>Sodickson, D.</creatorcontrib><creatorcontrib>Chen, T.Y.</creatorcontrib><creatorcontrib>Jurman, M.E.</creatorcontrib><title>An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding</title><title>Biophysical journal</title><addtitle>Biophys J</addtitle><description>Substitution of a cysteine in the extracellular mouth of the pore of the Shaker-delta K+ channel permits allosteric inhibition of the channel by Zn2+ or Cd2+ ions at micromolar concentrations. Cd2+ binds weakly to the open state but drives the channel into the slow (C-type) inactivated state, which has a Kd for Cd2+ of approximately 0.2 microM. There is a 45,000-fold increase in affinity when the channel changes from open to inactivated. These results indicate that C-type inactivation involves a structural change in the external mouth of the pore. This structural change is reflected in the T449C mutant as state-dependent metal affinity, which may result either from a change in proximity of the introduced cysteine residues of the four subunits or from a change of the exposure of this residue on the surface of the protein.</description><subject>Allosteric Regulation - genetics</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Biophysical Phenomena</subject><subject>Biophysics</subject><subject>Cadmium - metabolism</subject><subject>Cadmium - pharmacology</subject><subject>Cell Line</subject><subject>Cysteine - genetics</subject><subject>Cysteine - metabolism</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Models, Biological</subject><subject>Mutagenesis, Site-Directed</subject><subject>Potassium Channel Blockers</subject><subject>Potassium Channels - genetics</subject><subject>Potassium Channels - metabolism</subject><subject>Protein Binding</subject><subject>Protein Conformation</subject><subject>Protein Engineering</subject><subject>Zinc - metabolism</subject><issn>0006-3495</issn><issn>1542-0086</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFPGzEQha0KlAban4DkYxFaGO96vd4LVYRKW4HEAXq2bO9s4mpjU68TyL-vk6CInnqyrPfeN5p5hJwxuGTAxNUjAIii4m39peXnEqSUBf9ApqzmZQEgxRGZHiwfyck4_gZgZQ1sQiYSKlk17ZT8mXmKfu48YsSO2s2YMH-o8zQtkOJrwuj1QJdhlRY09FTTuwtqF9p7HKgehvAyZrO2ya11ciHHAjWY_d1q0CkjzYYuMWWEcb5zfv6JHPd6GPHz23tKft1-e7r5Udw_fP95M7svLBdlKkyPDVSC6xqMrlgja4OS9w3XouJWNp0pWymkYHUFGjmXvWHcABguTNeUUJ2S6z33eWWW2Fn0KepBPUe31HGjgnbqX8W7hZqHtWJlU0vGM6DeA2wM4xixP2QZqG0FaleB2t5XtVztKlDb3Nn7wYfU282z_nWvY95-7TCq0Tr0FjsX0SbVBfefCX8Bw7aYFA</recordid><startdate>19940401</startdate><enddate>19940401</enddate><creator>Yellen, G.</creator><creator>Sodickson, D.</creator><creator>Chen, T.Y.</creator><creator>Jurman, M.E.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>5PM</scope></search><sort><creationdate>19940401</creationdate><title>An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding</title><author>Yellen, G. ; Sodickson, D. ; Chen, T.Y. ; Jurman, M.E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-bfe70364a50ba31785be84f74a634c87db2986861530ae448fb14b00b46bd7203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Allosteric Regulation - genetics</topic><topic>Animals</topic><topic>Binding Sites</topic><topic>Biophysical Phenomena</topic><topic>Biophysics</topic><topic>Cadmium - metabolism</topic><topic>Cadmium - pharmacology</topic><topic>Cell Line</topic><topic>Cysteine - genetics</topic><topic>Cysteine - metabolism</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Models, Biological</topic><topic>Mutagenesis, Site-Directed</topic><topic>Potassium Channel Blockers</topic><topic>Potassium Channels - genetics</topic><topic>Potassium Channels - metabolism</topic><topic>Protein Binding</topic><topic>Protein Conformation</topic><topic>Protein Engineering</topic><topic>Zinc - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yellen, G.</creatorcontrib><creatorcontrib>Sodickson, D.</creatorcontrib><creatorcontrib>Chen, T.Y.</creatorcontrib><creatorcontrib>Jurman, M.E.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biophysical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yellen, G.</au><au>Sodickson, D.</au><au>Chen, T.Y.</au><au>Jurman, M.E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding</atitle><jtitle>Biophysical journal</jtitle><addtitle>Biophys J</addtitle><date>1994-04-01</date><risdate>1994</risdate><volume>66</volume><issue>4</issue><spage>1068</spage><epage>1075</epage><pages>1068-1075</pages><issn>0006-3495</issn><eissn>1542-0086</eissn><abstract>Substitution of a cysteine in the extracellular mouth of the pore of the Shaker-delta K+ channel permits allosteric inhibition of the channel by Zn2+ or Cd2+ ions at micromolar concentrations. Cd2+ binds weakly to the open state but drives the channel into the slow (C-type) inactivated state, which has a Kd for Cd2+ of approximately 0.2 microM. There is a 45,000-fold increase in affinity when the channel changes from open to inactivated. These results indicate that C-type inactivation involves a structural change in the external mouth of the pore. This structural change is reflected in the T449C mutant as state-dependent metal affinity, which may result either from a change in proximity of the introduced cysteine residues of the four subunits or from a change of the exposure of this residue on the surface of the protein.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>8038379</pmid><doi>10.1016/S0006-3495(94)80888-4</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0006-3495 |
| ispartof | Biophysical journal, 1994-04, Vol.66 (4), p.1068-1075 |
| issn | 0006-3495 1542-0086 |
| language | eng |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Allosteric Regulation - genetics Animals Binding Sites Biophysical Phenomena Biophysics Cadmium - metabolism Cadmium - pharmacology Cell Line Cysteine - genetics Cysteine - metabolism Humans Kinetics Models, Biological Mutagenesis, Site-Directed Potassium Channel Blockers Potassium Channels - genetics Potassium Channels - metabolism Protein Binding Protein Conformation Protein Engineering Zinc - metabolism |
| title | An engineered cysteine in the external mouth of a K+ channel allows inactivation to be modulated by metal binding |
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