Structural determinants of gating in the TRPV1 channel
Por:
Salazar, H, Jara-Oseguera, A, Hernandez-Garcia, E, Llorente, I, Arias-Olguin, II, Soriano-Garcia, M, Islas, LD, Rosenbaum, T
Publicada:
1 jul 2009
Resumen:
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.
Filiaciones:
Salazar, H:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biofis, Mexico City 04510, DF, Mexico
Jara-Oseguera, A:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City 04510, DF, Mexico
Hernandez-Garcia, E:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biofis, Mexico City 04510, DF, Mexico
Llorente, I:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biofis, Mexico City 04510, DF, Mexico
Arias-Olguin, II:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biofis, Mexico City 04510, DF, Mexico
Soriano-Garcia, M:
Univ Nacl Autonoma Mexico, Dept Bioquim, Inst Quim, Mexico City 04510, DF, Mexico
Islas, LD:
Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City 04510, DF, Mexico
Rosenbaum, T:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biofis, Mexico City 04510, DF, Mexico
|