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PMID: 19561608 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structural determinants of gating in the TRPV1 channel.

Nature structural & molecular biology ·Vol. 16 ·No. 7 ·2009-07-00 ·Pages 704-10

Salazar H, Jara-Oseguera A, Hernández-García E, Llorente I, Arias-Olguín II, Soriano-García M, Islas LD, Rosenbaum T

Abstract

Transient receptor potential vanilloid 1 (TRPV1) channels mediate several types of physiological responses. Despite the importance of these channels in pain detection and inflammation, little is known about how their structural components convert different types of stimuli into channel activity. To localize the activation gate of these channels, we inserted cysteines along the S6 segment of mutant TRPV1 channels and assessed their accessibility to thiol-modifying agents. We show that access to the pore of TRPV1 is gated by S6 in response to both capsaicin binding and increases in temperature, that the pore-forming S6 segments are helical structures and that two constrictions are present in the pore: one that impedes the access of large molecules and the other that hampers the access of smaller ions and constitutes an activation gate of these channels.

MeSH Terms
Amino Acid Sequence Animals Capsaicin/metabolism Cysteine/chemistry Ion Channel Gating/physiology Ions/metabolism Leucine/chemistry Mesylates/chemistry Models, Molecular Molecular Sequence Data Protein Structure, Secondary Protein Structure, Tertiary Rats Sensory System Agents/metabolism TRPV Cation Channels/chemistry,genetics,metabolism Temperature Tyrosine/chemistry
Chemicals
Ions Mesylates Sensory System Agents TRPV Cation Channels Trpv1 protein, rat Tyrosine Leucine Cysteine Capsaicin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Salazar Héctor
Departamento de Biofísica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F., México.
Jara-Oseguera Andrés
Hernández-García Enrique
Llorente Itzel
Arias-Olguín Imilla I
Soriano-García Manuel
Islas León D
Rosenbaum Tamara
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1633
Published
2009-07-00
Epub
2009-00-28
Pages
704-10
Language
English
Region
United States
NLM ID
101186374
Subset
IM
External Links
PubMed source DOI: 10.1038/nsmb.1633 View journal details
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