Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel-Reference-Cited by-同舟云学术

Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel

Published:2019-03 Issue:6430 Volume:363 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Yin Ying¹^ORCID,Le Son C.¹^ORCID,Hsu Allen L.²^ORCID,Borgnia Mario J.¹²^ORCID,Yang Huanghe¹^ORCID,Lee Seok-Yong¹^ORCID

Affiliation:

1. Department of Biochemistry, Duke University School of Medicine, Durham, NC, 27710, USA.

2. Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.

Abstract

Cool mechanism for sensing cool In humans, cold is primarily sensed by transient receptor potential melastatin member 8 (TRPM8), a calcium channel. Yin et al. present cryo–electron microscopy structures of TRPM8 with cooling agents, membrane lipid phosphatidylinositol-4,5-bisphosphate (PIP2), and calcium. Structural and functional analyses showed that the PIP2 binding site in TRPM8 is completely different from PIP2 sites in other TRP channels. The binding of PIP2 and cooling agents allosterically enhance each other and activate the channel opening. Thus, the activation mechanism of TRPM8 is distinct from that used by other TRP channels. Science , this issue p. eaav9334

Funder

National Institute of General Medical Sciences

National Institute of Neurological Disorders and Stroke

National Institute of Environmental Health Sciences

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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