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Updated: Sep 21, 2025

Purification and Reconstitution of TRPV1 for Spectroscopic Analysis
Published on: July 3, 2018
The crystal structure of TRPM2 MHR1/2 domain reveals a conserved Zn2+ -binding domain essential for structural
Simon Sander1, Jelena Pick2, Ellen Gattkowski1
1Hamburg Advanced Research Centre for Bioorganic Chemistry (HARBOR) & Department of Chemistry, Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany.
Abstract:
Transient receptor potential melastatin 2 (TRPM2) is a Ca2+ -permeable, nonselective cation channel involved in diverse physiological processes such as immune response, apoptosis, and body temperature sensing. TRPM2 is activated by ADP-ribose (ADPR) and 2'-deoxy-ADPR in a Ca2+ -dependent manner. While two distinct binding sites exist for ADPR that exert different functions dependent on the species, the involvement of either binding site regarding the superagonistic effect of 2'-deoxy-ADPR is not clear yet. Here, we report the crystal structure of the MHR1/2 domain of TRPM2 from zebrafish (Danio rerio), and show that both ligands bind to this domain and activate the channel. We identified a so far unrecognized Zn2+ -binding domain that was not resolved in previous cryo-EM structures and that is conserved in most TRPM channels. In combination with patch clamp experiments we comprehensively characterize the effect of the Zn2+ -binding domain on TRPM2 activation. Our results provide insight into a conserved motif essential for structural integrity and channel activity.
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