Human TRPC5 structures reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site

David J. Wright; Katie J. Simmons; Rachel M. Johnson; David J. Beech; Stephen P. Muench; Robin S. Bon

doi:10.1038/s42003-020-01437-8

Communications Biology (Nov 2020)

Human TRPC5 structures reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site

David J. Wright,
Katie J. Simmons,
Rachel M. Johnson,
David J. Beech,
Stephen P. Muench,
Robin S. Bon

Affiliations

David J. Wright: Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds
Katie J. Simmons: Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds
Rachel M. Johnson: Astbury Centre for Structural Molecular Biology, University of Leeds
David J. Beech: Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds
Stephen P. Muench: Astbury Centre for Structural Molecular Biology, University of Leeds
Robin S. Bon: Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds

DOI: https://doi.org/10.1038/s42003-020-01437-8
Journal volume & issue: Vol. 3, no. 1
pp. 1 – 11

Abstract

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Wright et al. report the first structure of a human TRPC1/4/5 channel in complex with a xanthine-based TRPC5 inhibitor Pico145. They find that Pico145 binds to a conserved lipid binding site of TRPC5, where it displaces a phospholipid. This study provides insights into the mechanism-of-action of xanthine-based TRPC1/4/5 modulators.

Published in Communications Biology

ISSN: 2399-3642 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General)
Website: https://www.nature.com/commsbio/

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