Article abstract
Nature Structural & Molecular Biology 16, 704 - 710 (2009)
Published online: 28 June 2009 | doi:10.1038/nsmb.1633
Structural determinants of gating in the TRPV1 channel
Héctor Salazar1,4, Andrés Jara-Oseguera2,4, Enrique Hernández-García1,4, Itzel Llorente1, Imilla I Arias-Olguín1, Manuel Soriano-García3, León D Islas2 & Tamara Rosenbaum1
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.
- Departamento de Biofísica, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F., México.
- Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., México.
- Departamento de Bioquímica, Instituto de Química, Universidad Nacional Autónoma de México, México, D.F., México.
- These authors contributed equally to this work.
Correspondence to: Tamara Rosenbaum1 e-mail: trosenba@ifc.unam.mx
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