Structures and gating mechanism of human TRPM2

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25/11/2018

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1 minute

Transient receptor potential (TRP) melastatin 2 (TRPM2) is a cation channel associated with numerous diseases. It has a C-terminal NUDT9 homology (NUDT9H) domain responsible for binding ADP-ribose (ADPR), and both ADPR and Ca²⁺ are required for TRPM2 activation. Here we report cryo-EM structures of human TRPM2, alone, with ADPR, and with ADPR and Ca²⁺.

NUDT9H forms both intra- and inter-subunit interactions with the N-terminal TRPM homology region (MHR1/2/3) in the apo state, but undergoes conformational changes upon ADPR binding, resulting in rotation of MHR1/2 and disruption of the inter-subunit interaction. Ca²⁺ binding further engages transmembrane helices and the conserved TRP helix to cause conformational changes at the MHR arm and the lower gating pore to potentiate channel opening.

These findings explain the molecular mechanism of concerted TRPM2 gating by ADPR and Ca²⁺ and provide insights into the gating mechanism of other TRP channels.

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Pavlos Papadopoulos

Pavlos Papadopoulos is a Senior Field Engineer and long-time technology enthusiast based in Thessaloniki, Greece. With over a decade of hands-on experience working with hardware, software, mobile devices, and real-world IT systems, he brings a practical, engineer-level perspective to every article he writes.A passionate smartphone user—especially within the Xiaomi ecosystem—Pavlos explores how apps, tools, and everyday technologies perform in real use. His interests span programming, web development, DIY tech projects, digital workflows, and productivity tools.He is also the founder and editor of three technology websites: Gadget Rumours, TheLatestTechNews, and TechnologyNews.info, where he has written and curated more than a thousand articles covering software, mobile tech, hardware, and emerging digital trends.Pavlos is committed to clear explanations, helpful guides, and honest, experience-based insights that help readers make better decisions about the technology they use every day.

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