The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism
Transient receptor potential vanilloid subfamily member 3 (TRPV3) is a temperature-sensitive cation channel. Previous cryo-EM analyses of TRPV3 in detergent micelles or amphipol proposed that the lower gate opens by α-to-π helical transitions of the nearby S6 helix. However, it remains unclear how p...
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| Veröffentlicht in: | Nature structural & molecular biology 2020-07, Vol.27 (7), p.645-652 |
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| creator | Shimada, Hiroto Kusakizako, Tsukasa Dung Nguyen, T. H. Nishizawa, Tomohiro Hino, Tomoya Tominaga, Makoto Nureki, Osamu |
| description | Transient receptor potential vanilloid subfamily member 3 (TRPV3) is a temperature-sensitive cation channel. Previous cryo-EM analyses of TRPV3 in detergent micelles or amphipol proposed that the lower gate opens by α-to-π helical transitions of the nearby S6 helix. However, it remains unclear how physiological lipids are involved in the TRPV3 activation. Here we determined the apo state structure of mouse (
Mus musculus
) TRPV3 in a lipid nanodisc at 3.3 Å resolution. The structure revealed that lipids bound to the pore domain stabilize the selectivity filter in the narrow state, suggesting that the selectivity filter of TRPV3 affects cation permeation. When the lower gate is closed in nanodisc-reconstituted TRPV3, the S6 helix adopts the π-helical conformation without agonist- or heat-sensitization, potentially stabilized by putative intra-subunit hydrogen bonds and lipid binding. Our findings provide insights into the lipid-associated gating mechanism of TRPV3.
A cryo-EM structure of mouse TRPV3 in nanodiscs reveal lipids bound to the pore domain, stabilizing the selectivity filter in the narrow state and the S6 in a π-helical conformation. |
| doi_str_mv | 10.1038/s41594-020-0439-z |
| format | Article |
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Mus musculus
) TRPV3 in a lipid nanodisc at 3.3 Å resolution. The structure revealed that lipids bound to the pore domain stabilize the selectivity filter in the narrow state, suggesting that the selectivity filter of TRPV3 affects cation permeation. When the lower gate is closed in nanodisc-reconstituted TRPV3, the S6 helix adopts the π-helical conformation without agonist- or heat-sensitization, potentially stabilized by putative intra-subunit hydrogen bonds and lipid binding. Our findings provide insights into the lipid-associated gating mechanism of TRPV3.
A cryo-EM structure of mouse TRPV3 in nanodiscs reveal lipids bound to the pore domain, stabilizing the selectivity filter in the narrow state and the S6 in a π-helical conformation.</description><identifier>ISSN: 1545-9993</identifier><identifier>EISSN: 1545-9985</identifier><identifier>DOI: 10.1038/s41594-020-0439-z</identifier><identifier>PMID: 32572254</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>101/28 ; 631/535/1258 ; 631/57/2270/1140 ; 9/74 ; Biochemistry ; Biological Microscopy ; Biomedical and Life Sciences ; Cations ; Channel gating ; Conformation ; Cryoelectron Microscopy ; Domains ; Hydrogen Bonding ; Hydrogen bonds ; Ion Channel Gating - physiology ; Ion channels ; Ions ; Life Sciences ; Lipids ; Lipids - chemistry ; Membrane Biology ; Micelles ; Models, Molecular ; Nanostructures - chemistry ; Protein Conformation ; Protein Structure ; Selectivity ; Transient receptor potential proteins ; TRPV Cation Channels - chemistry ; TRPV Cation Channels - metabolism</subject><ispartof>Nature structural & molecular biology, 2020-07, Vol.27 (7), p.645-652</ispartof><rights>This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020</rights><rights>This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-5c96c5a59079d85100e97a73dfdce179a13f09e608a4358100d54195af2a9ec3</citedby><cites>FETCH-LOGICAL-c438t-5c96c5a59079d85100e97a73dfdce179a13f09e608a4358100d54195af2a9ec3</cites><orcidid>0000-0003-1813-7008 ; 0000-0002-8813-4622 ; 0000-0002-6186-6647 ; 0000-0001-7463-8398 ; 0000-0003-3111-3772</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41594-020-0439-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41594-020-0439-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32572254$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shimada, Hiroto</creatorcontrib><creatorcontrib>Kusakizako, Tsukasa</creatorcontrib><creatorcontrib>Dung Nguyen, T. H.</creatorcontrib><creatorcontrib>Nishizawa, Tomohiro</creatorcontrib><creatorcontrib>Hino, Tomoya</creatorcontrib><creatorcontrib>Tominaga, Makoto</creatorcontrib><creatorcontrib>Nureki, Osamu</creatorcontrib><title>The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism</title><title>Nature structural & molecular biology</title><addtitle>Nat Struct Mol Biol</addtitle><addtitle>Nat Struct Mol Biol</addtitle><description>Transient receptor potential vanilloid subfamily member 3 (TRPV3) is a temperature-sensitive cation channel. Previous cryo-EM analyses of TRPV3 in detergent micelles or amphipol proposed that the lower gate opens by α-to-π helical transitions of the nearby S6 helix. However, it remains unclear how physiological lipids are involved in the TRPV3 activation. Here we determined the apo state structure of mouse (
Mus musculus
) TRPV3 in a lipid nanodisc at 3.3 Å resolution. The structure revealed that lipids bound to the pore domain stabilize the selectivity filter in the narrow state, suggesting that the selectivity filter of TRPV3 affects cation permeation. When the lower gate is closed in nanodisc-reconstituted TRPV3, the S6 helix adopts the π-helical conformation without agonist- or heat-sensitization, potentially stabilized by putative intra-subunit hydrogen bonds and lipid binding. Our findings provide insights into the lipid-associated gating mechanism of TRPV3.
A cryo-EM structure of mouse TRPV3 in nanodiscs reveal lipids bound to the pore domain, stabilizing the selectivity filter in the narrow state and the S6 in a π-helical conformation.</description><subject>101/28</subject><subject>631/535/1258</subject><subject>631/57/2270/1140</subject><subject>9/74</subject><subject>Biochemistry</subject><subject>Biological Microscopy</subject><subject>Biomedical and Life Sciences</subject><subject>Cations</subject><subject>Channel gating</subject><subject>Conformation</subject><subject>Cryoelectron Microscopy</subject><subject>Domains</subject><subject>Hydrogen Bonding</subject><subject>Hydrogen bonds</subject><subject>Ion Channel Gating - physiology</subject><subject>Ion channels</subject><subject>Ions</subject><subject>Life Sciences</subject><subject>Lipids</subject><subject>Lipids - chemistry</subject><subject>Membrane Biology</subject><subject>Micelles</subject><subject>Models, Molecular</subject><subject>Nanostructures - chemistry</subject><subject>Protein Conformation</subject><subject>Protein Structure</subject><subject>Selectivity</subject><subject>Transient receptor potential proteins</subject><subject>TRPV Cation Channels - chemistry</subject><subject>TRPV Cation Channels - metabolism</subject><issn>1545-9993</issn><issn>1545-9985</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp1kFtLwzAUx4Mobk4_gC9S8Dma69o8yvAGA4cUX0NMTreOtZ1JKrhPb0Z1Pvl0Dvxv8EPokpIbSnhxGwSVSmDCCCaCK7w7QmMqhcRKFfL48Cs-QmchrAlhUub8FI04kzljUozRolxBFqLvbew9ZF2Vbept7bLWtJ2rg8UebNeGWMc-gsvK18Ubzzx8gtmELKbs0sS6XWYN2JVp69Cco5MqaXDxcyeofLgvZ094_vL4PLubYyt4EbG0amqlkYrkyhWSEgIqNzl3lbNAc2Uor4iCKSmM4LJIupOCKmkqZhRYPkHXQ-3Wdx89hKjXXe_btKiZYHTKaaFEctHBZX0XgodKb33dGP-lKdF7hHpAqBNCvUeodylz9dPcvzfgDolfZsnABkNIUrsE_zf9f-s35c58Hg</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Shimada, Hiroto</creator><creator>Kusakizako, Tsukasa</creator><creator>Dung Nguyen, T. 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H.</au><au>Nishizawa, Tomohiro</au><au>Hino, Tomoya</au><au>Tominaga, Makoto</au><au>Nureki, Osamu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism</atitle><jtitle>Nature structural & molecular biology</jtitle><stitle>Nat Struct Mol Biol</stitle><addtitle>Nat Struct Mol Biol</addtitle><date>2020-07-01</date><risdate>2020</risdate><volume>27</volume><issue>7</issue><spage>645</spage><epage>652</epage><pages>645-652</pages><issn>1545-9993</issn><eissn>1545-9985</eissn><abstract>Transient receptor potential vanilloid subfamily member 3 (TRPV3) is a temperature-sensitive cation channel. Previous cryo-EM analyses of TRPV3 in detergent micelles or amphipol proposed that the lower gate opens by α-to-π helical transitions of the nearby S6 helix. However, it remains unclear how physiological lipids are involved in the TRPV3 activation. Here we determined the apo state structure of mouse (
Mus musculus
) TRPV3 in a lipid nanodisc at 3.3 Å resolution. The structure revealed that lipids bound to the pore domain stabilize the selectivity filter in the narrow state, suggesting that the selectivity filter of TRPV3 affects cation permeation. When the lower gate is closed in nanodisc-reconstituted TRPV3, the S6 helix adopts the π-helical conformation without agonist- or heat-sensitization, potentially stabilized by putative intra-subunit hydrogen bonds and lipid binding. Our findings provide insights into the lipid-associated gating mechanism of TRPV3.
A cryo-EM structure of mouse TRPV3 in nanodiscs reveal lipids bound to the pore domain, stabilizing the selectivity filter in the narrow state and the S6 in a π-helical conformation.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>32572254</pmid><doi>10.1038/s41594-020-0439-z</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-1813-7008</orcidid><orcidid>https://orcid.org/0000-0002-8813-4622</orcidid><orcidid>https://orcid.org/0000-0002-6186-6647</orcidid><orcidid>https://orcid.org/0000-0001-7463-8398</orcidid><orcidid>https://orcid.org/0000-0003-3111-3772</orcidid></addata></record> |
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| subjects | 101/28 631/535/1258 631/57/2270/1140 9/74 Biochemistry Biological Microscopy Biomedical and Life Sciences Cations Channel gating Conformation Cryoelectron Microscopy Domains Hydrogen Bonding Hydrogen bonds Ion Channel Gating - physiology Ion channels Ions Life Sciences Lipids Lipids - chemistry Membrane Biology Micelles Models, Molecular Nanostructures - chemistry Protein Conformation Protein Structure Selectivity Transient receptor potential proteins TRPV Cation Channels - chemistry TRPV Cation Channels - metabolism |
| title | The structure of lipid nanodisc-reconstituted TRPV3 reveals the gating mechanism |
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