Publication:
Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel

Дата
2021
Авторы
Nadezhdin, K. D.
Neuberger, A.
Krylov, N. A.
Sinica, V.
Trofimov, Y. A.
Journal Title
Journal ISSN
Volume Title
Издатель
Научные группы
Организационные подразделения
Организационная единица
Институт ядерной физики и технологий
Цель ИЯФиТ и стратегия развития - создание и развитие научно-образовательного центра мирового уровня в области ядерной физики и технологий, радиационного материаловедения, физики элементарных частиц, астрофизики и космофизики.
Выпуск журнала
Аннотация
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.Numerous physiological functions rely on distinguishing temperature through temperature-sensitive transient receptor potential channels (thermo-TRPs). Although the function of thermo-TRPs has been studied extensively, structural determination of their heat- and cold-activated states has remained a challenge. Here, we present cryo-EM structures of the nanodisc-reconstituted wild-type mouse TRPV3 in three distinct conformations: closed, heat-activated sensitized and open states. The heat-induced transformations of TRPV3 are accompanied by changes in the secondary structure of the S2-S3 linker and the N and C termini and represent a conformational wave that links these parts of the protein to a lipid occupying the vanilloid binding site. State-dependent differences in the behavior of bound lipids suggest their active role in thermo-TRP temperature-dependent gating. Our structural data, supported by physiological recordings and molecular dynamics simulations, provide an insight for understanding the molecular mechanism of temperature sensing.
Описание
Ключевые слова
Цитирование
Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel / Nadezhdin, K.D. [et al.] // Nature Structural and Molecular Biology. - 2021. - 10.1038/s41594-021-00615-4
Коллекции