7AOV

Crystal Structure of a TRPM2 Domain

Summary for 7AOV

• Entry DOI: 10.2210/pdb7aov/pdb
• Descriptor: Transient receptor potential cation channel subfamily M member 2, ZINC ION (3 entities in total)
• Functional Keywords: trpm2, signaling protein
• Biological source: Danio rerio (Zebrafish, Brachydanio rerio)
• Total number of polymer chains: 2
• Total formula weight: 96125.87

Authors

Sander, S.,Tidow, H. (deposition date: 2020-10-15, release date: 2022-03-02, Last modification date: 2024-11-06)

Primary citation

Sander, S.,Pick, J.,Gattkowski, E.,Fliegert, R.,Tidow, H.
The crystal structure of TRPM2 MHR1/2 domain reveals a conserved Zn 2+ -binding domain essential for structural integrity and channel activity.
Protein Sci., 31:e4320-e4320, 2022

PubMed Abstract: Transient receptor potential melastatin 2 (TRPM2) is a Ca -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 Ca -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 Zn -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 Zn -binding domain on TRPM2 activation. Our results provide insight into a conserved motif essential for structural integrity and channel activity.

PubMed: 35634784
DOI: 10.1002/pro.4320

Experimental method

X-RAY DIFFRACTION (2.00001625778 Å)