Loading…

Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors)

P2X receptors are trimeric cation channels with widespread roles in health and disease. The recent crystal structure of a P2X4 receptor provides a 3D view of their topology and architecture. A key unresolved issue is how ions gain access to the pore, because the structure reveals two different pathw...

Full description

Saved in:

Bibliographic Details
Published in:	Proceedings of the National Academy of Sciences - PNAS 2011-08, Vol.108 (33), p.13800-13805
Main Authors:	Samways, Damien S. K, Khakh, Baljit S, Dutertre, Sébastien, Egan, Terrance M
Format:	Article
Language:	English
Subjects:	Access routes Adenosine Triphosphate Biochemistry, Molecular Biology Biological Sciences Cations Cells Crystal structure Diffusion Electric current Electrochemistry HEK293 cells Humans Ion Channel Gating Ion channels Ion currents Ions Ions - metabolism Life Sciences Membrane Potentials - physiology Models, Molecular Neurobiology Neurons Neurons and Cognition Neuroscience Pharmaceutical sciences Pharmacology Protein Structure, Tertiary Proteins Reagents Receptors Receptors, Purinergic P2X4 - chemistry Receptors, Purinergic P2X4 - physiology Signal transduction spatial distribution Structural Biology Topology
Citations:	Items that this one cites Items that cite this one
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

cited_by	cdi_FETCH-LOGICAL-c590t-1bd4ce856de7d3e08311298a563f4743e74324b378f04430170ac5a9f7e7d2723
cites	cdi_FETCH-LOGICAL-c590t-1bd4ce856de7d3e08311298a563f4743e74324b378f04430170ac5a9f7e7d2723
container_end_page	13805
container_issue	33
container_start_page	13800
container_title	Proceedings of the National Academy of Sciences - PNAS
container_volume	108
creator	Samways, Damien S. K Khakh, Baljit S Dutertre, Sébastien Egan, Terrance M
description	P2X receptors are trimeric cation channels with widespread roles in health and disease. The recent crystal structure of a P2X4 receptor provides a 3D view of their topology and architecture. A key unresolved issue is how ions gain access to the pore, because the structure reveals two different pathways within the extracellular domain. One of these is the central pathway spanning the entire length of the extracellular domain and covering a distance of ≈70 Å. The second consists of three lateral portals, adjacent to the membrane and connected to the transmembrane pore by short tunnels. Here, we demonstrate the preferential use of the lateral portals. Owing to their favorable diameters and equivalent spacing, the lateral portals split the task of ion supply threefold and minimize an ion's diffusive path before it succumbs to transmembrane electrochemical gradients.
doi_str_mv	10.1073/pnas.1017550108
format	article
fullrecord	<record><control><sourceid>jstor_pnas_</sourceid><recordid>TN_cdi_pnas_primary_108_33_13800</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>27979278</jstor_id><sourcerecordid>27979278</sourcerecordid><originalsourceid>FETCH-LOGICAL-c590t-1bd4ce856de7d3e08311298a563f4743e74324b378f04430170ac5a9f7e7d2723</originalsourceid><addsrcrecordid>eNpdkk1vEzEQhlcIREPhzAmwuEAPS8cfu7YvSFEFFCkSkWglbpbjeJONkvVieytx46czm4QGerBseZ73HY9niuIlhQ8UJL_sO5vwRGVVAQX1qJhQ0LSshYbHxQSAyVIJJs6KZyltAEBXCp4WZ4wqUEDVpPg9j77x0Xe5tVsyJE9CQ4YuLFKOg8t-SbY2-4ixPsRst4nYRPLaE-ucT4nEMGRPctjfIbLXr4ed7cj0Zl6u7GjRho64te06j_r3c_aDRO98n0NMF8-LJw3a-hfH_by4_fzp5uq6nH378vVqOitdpSGXdLEUzquqXnq55B4Up5RpZauaN0IK7nExseBSNSAExx8B6yqrG4k8k4yfFx8Pvv2w2Pmlw4qxKtPHdmfjLxNsa_6PdO3arMKd4bRSVGo0uDgYrB_IrqczM94B41ArLe4osu-OyWL4OfiUza5Nzm-3tvNhSEZhU2qNPUPy7QNyE4bY4U_sIa0rqRC6PEAuhpSwYff5KZhxDsw4B-Y0B6h4_W-19_zfxiNAjsCoPNkpw7mhXMH4tFcHZJOwUycLqaVm-1e9OcQbG4xdxTaZ2-8MqMA5wyw18D-nq8tE</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>884299578</pqid></control><display><type>article</type><title>Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors)</title><source>JSTOR Archival Journals</source><source>PubMed Central</source><creator>Samways, Damien S. K ; Khakh, Baljit S ; Dutertre, Sébastien ; Egan, Terrance M</creator><creatorcontrib>Samways, Damien S. K ; Khakh, Baljit S ; Dutertre, Sébastien ; Egan, Terrance M</creatorcontrib><description>P2X receptors are trimeric cation channels with widespread roles in health and disease. The recent crystal structure of a P2X4 receptor provides a 3D view of their topology and architecture. A key unresolved issue is how ions gain access to the pore, because the structure reveals two different pathways within the extracellular domain. One of these is the central pathway spanning the entire length of the extracellular domain and covering a distance of ≈70 Å. The second consists of three lateral portals, adjacent to the membrane and connected to the transmembrane pore by short tunnels. Here, we demonstrate the preferential use of the lateral portals. Owing to their favorable diameters and equivalent spacing, the lateral portals split the task of ion supply threefold and minimize an ion's diffusive path before it succumbs to transmembrane electrochemical gradients.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1017550108</identifier><identifier>PMID: 21808018</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Access routes ; Adenosine Triphosphate ; Biochemistry, Molecular Biology ; Biological Sciences ; Cations ; Cells ; Crystal structure ; Diffusion ; Electric current ; Electrochemistry ; HEK293 cells ; Humans ; Ion Channel Gating ; Ion channels ; Ion currents ; Ions ; Ions - metabolism ; Life Sciences ; Membrane Potentials - physiology ; Models, Molecular ; Neurobiology ; Neurons ; Neurons and Cognition ; Neuroscience ; Pharmaceutical sciences ; Pharmacology ; Protein Structure, Tertiary ; Proteins ; Reagents ; Receptors ; Receptors, Purinergic P2X4 - chemistry ; Receptors, Purinergic P2X4 - physiology ; Signal transduction ; spatial distribution ; Structural Biology ; Topology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2011-08, Vol.108 (33), p.13800-13805</ispartof><rights>copyright © 1993–2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Aug 16, 2011</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c590t-1bd4ce856de7d3e08311298a563f4743e74324b378f04430170ac5a9f7e7d2723</citedby><cites>FETCH-LOGICAL-c590t-1bd4ce856de7d3e08311298a563f4743e74324b378f04430170ac5a9f7e7d2723</cites><orcidid>0000-0002-2945-1484</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/108/33.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/27979278$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/27979278$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793,58238,58471</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21808018$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02306894$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Samways, Damien S. K</creatorcontrib><creatorcontrib>Khakh, Baljit S</creatorcontrib><creatorcontrib>Dutertre, Sébastien</creatorcontrib><creatorcontrib>Egan, Terrance M</creatorcontrib><title>Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors)</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>P2X receptors are trimeric cation channels with widespread roles in health and disease. The recent crystal structure of a P2X4 receptor provides a 3D view of their topology and architecture. A key unresolved issue is how ions gain access to the pore, because the structure reveals two different pathways within the extracellular domain. One of these is the central pathway spanning the entire length of the extracellular domain and covering a distance of ≈70 Å. The second consists of three lateral portals, adjacent to the membrane and connected to the transmembrane pore by short tunnels. Here, we demonstrate the preferential use of the lateral portals. Owing to their favorable diameters and equivalent spacing, the lateral portals split the task of ion supply threefold and minimize an ion's diffusive path before it succumbs to transmembrane electrochemical gradients.</description><subject>Access routes</subject><subject>Adenosine Triphosphate</subject><subject>Biochemistry, Molecular Biology</subject><subject>Biological Sciences</subject><subject>Cations</subject><subject>Cells</subject><subject>Crystal structure</subject><subject>Diffusion</subject><subject>Electric current</subject><subject>Electrochemistry</subject><subject>HEK293 cells</subject><subject>Humans</subject><subject>Ion Channel Gating</subject><subject>Ion channels</subject><subject>Ion currents</subject><subject>Ions</subject><subject>Ions - metabolism</subject><subject>Life Sciences</subject><subject>Membrane Potentials - physiology</subject><subject>Models, Molecular</subject><subject>Neurobiology</subject><subject>Neurons</subject><subject>Neurons and Cognition</subject><subject>Neuroscience</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacology</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins</subject><subject>Reagents</subject><subject>Receptors</subject><subject>Receptors, Purinergic P2X4 - chemistry</subject><subject>Receptors, Purinergic P2X4 - physiology</subject><subject>Signal transduction</subject><subject>spatial distribution</subject><subject>Structural Biology</subject><subject>Topology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNpdkk1vEzEQhlcIREPhzAmwuEAPS8cfu7YvSFEFFCkSkWglbpbjeJONkvVieytx46czm4QGerBseZ73HY9niuIlhQ8UJL_sO5vwRGVVAQX1qJhQ0LSshYbHxQSAyVIJJs6KZyltAEBXCp4WZ4wqUEDVpPg9j77x0Xe5tVsyJE9CQ4YuLFKOg8t-SbY2-4ixPsRst4nYRPLaE-ucT4nEMGRPctjfIbLXr4ed7cj0Zl6u7GjRho64te06j_r3c_aDRO98n0NMF8-LJw3a-hfH_by4_fzp5uq6nH378vVqOitdpSGXdLEUzquqXnq55B4Up5RpZauaN0IK7nExseBSNSAExx8B6yqrG4k8k4yfFx8Pvv2w2Pmlw4qxKtPHdmfjLxNsa_6PdO3arMKd4bRSVGo0uDgYrB_IrqczM94B41ArLe4osu-OyWL4OfiUza5Nzm-3tvNhSEZhU2qNPUPy7QNyE4bY4U_sIa0rqRC6PEAuhpSwYff5KZhxDsw4B-Y0B6h4_W-19_zfxiNAjsCoPNkpw7mhXMH4tFcHZJOwUycLqaVm-1e9OcQbG4xdxTaZ2-8MqMA5wyw18D-nq8tE</recordid><startdate>20110816</startdate><enddate>20110816</enddate><creator>Samways, Damien S. K</creator><creator>Khakh, Baljit S</creator><creator>Dutertre, Sébastien</creator><creator>Egan, Terrance M</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2945-1484</orcidid></search><sort><creationdate>20110816</creationdate><title>Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors)</title><author>Samways, Damien S. K ; Khakh, Baljit S ; Dutertre, Sébastien ; Egan, Terrance M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c590t-1bd4ce856de7d3e08311298a563f4743e74324b378f04430170ac5a9f7e7d2723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Access routes</topic><topic>Adenosine Triphosphate</topic><topic>Biochemistry, Molecular Biology</topic><topic>Biological Sciences</topic><topic>Cations</topic><topic>Cells</topic><topic>Crystal structure</topic><topic>Diffusion</topic><topic>Electric current</topic><topic>Electrochemistry</topic><topic>HEK293 cells</topic><topic>Humans</topic><topic>Ion Channel Gating</topic><topic>Ion channels</topic><topic>Ion currents</topic><topic>Ions</topic><topic>Ions - metabolism</topic><topic>Life Sciences</topic><topic>Membrane Potentials - physiology</topic><topic>Models, Molecular</topic><topic>Neurobiology</topic><topic>Neurons</topic><topic>Neurons and Cognition</topic><topic>Neuroscience</topic><topic>Pharmaceutical sciences</topic><topic>Pharmacology</topic><topic>Protein Structure, Tertiary</topic><topic>Proteins</topic><topic>Reagents</topic><topic>Receptors</topic><topic>Receptors, Purinergic P2X4 - chemistry</topic><topic>Receptors, Purinergic P2X4 - physiology</topic><topic>Signal transduction</topic><topic>spatial distribution</topic><topic>Structural Biology</topic><topic>Topology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Samways, Damien S. K</creatorcontrib><creatorcontrib>Khakh, Baljit S</creatorcontrib><creatorcontrib>Dutertre, Sébastien</creatorcontrib><creatorcontrib>Egan, Terrance M</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Samways, Damien S. K</au><au>Khakh, Baljit S</au><au>Dutertre, Sébastien</au><au>Egan, Terrance M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors)</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2011-08-16</date><risdate>2011</risdate><volume>108</volume><issue>33</issue><spage>13800</spage><epage>13805</epage><pages>13800-13805</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>P2X receptors are trimeric cation channels with widespread roles in health and disease. The recent crystal structure of a P2X4 receptor provides a 3D view of their topology and architecture. A key unresolved issue is how ions gain access to the pore, because the structure reveals two different pathways within the extracellular domain. One of these is the central pathway spanning the entire length of the extracellular domain and covering a distance of ≈70 Å. The second consists of three lateral portals, adjacent to the membrane and connected to the transmembrane pore by short tunnels. Here, we demonstrate the preferential use of the lateral portals. Owing to their favorable diameters and equivalent spacing, the lateral portals split the task of ion supply threefold and minimize an ion's diffusive path before it succumbs to transmembrane electrochemical gradients.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>21808018</pmid><doi>10.1073/pnas.1017550108</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-2945-1484</orcidid><oa>free_for_read</oa></addata></record>
fulltext	fulltext
identifier	ISSN: 0027-8424
ispartof	Proceedings of the National Academy of Sciences - PNAS, 2011-08, Vol.108 (33), p.13800-13805
issn	0027-8424 1091-6490
language	eng
recordid	cdi_pnas_primary_108_33_13800
source	JSTOR Archival Journals; PubMed Central
subjects	Access routes Adenosine Triphosphate Biochemistry, Molecular Biology Biological Sciences Cations Cells Crystal structure Diffusion Electric current Electrochemistry HEK293 cells Humans Ion Channel Gating Ion channels Ion currents Ions Ions - metabolism Life Sciences Membrane Potentials - physiology Models, Molecular Neurobiology Neurons Neurons and Cognition Neuroscience Pharmaceutical sciences Pharmacology Protein Structure, Tertiary Proteins Reagents Receptors Receptors, Purinergic P2X4 - chemistry Receptors, Purinergic P2X4 - physiology Signal transduction spatial distribution Structural Biology Topology
title	Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors)
url	http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T13%3A05%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pnas_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Preferential%20use%20of%20unobstructed%20lateral%20portals%20as%20the%20access%20route%20to%20the%20pore%20of%20human%20ATP-gated%20ion%20channels%20(P2X%20receptors)&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Samways,%20Damien%20S.%20K&rft.date=2011-08-16&rft.volume=108&rft.issue=33&rft.spage=13800&rft.epage=13805&rft.pages=13800-13805&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.1017550108&rft_dat=%3Cjstor_pnas_%3E27979278%3C/jstor_pnas_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c590t-1bd4ce856de7d3e08311298a563f4743e74324b378f04430170ac5a9f7e7d2723%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=884299578&rft_id=info:pmid/21808018&rft_jstor_id=27979278&rfr_iscdi=true