Iordanov, Iordan and Tóth, Balázs and Szollosi, Andras and Csanády, László (2019) Enzyme activity and selectivity filter stability of ancient TRPM2 channels were simultaneously lost in early vertebrates. eLife, 8. e44556. ISSN 2050-084X
This is the latest version of this item.
|
Text
elife-44556-v2 (2).pdf Download (3MB) | Preview |
Abstract
Transient Receptor Potential Melastatin 2 (TRPM2) is a cation channel important for the immune response, insulin secretion, and body temperature regulation. It is activated by cytosolic ADP ribose (ADPR) and contains a nudix-type motif 9 (NUDT9)-homology (NUDT9-H) domain homologous to ADPR phosphohydrolases (ADPRases). Human TRPM2 (hsTRPM2) is catalytically inactive due to mutations in the conserved Nudix box sequence. Here, we show that TRPM2 Nudix motifs are canonical in all invertebrates but vestigial in vertebrates. Correspondingly, TRPM2 of the cnidarian Nematostella vectensis (nvTRPM2) and the choanoflagellate Salpingoeca rosetta (srTRPM2) are active ADPRases. Disruption of ADPRase activity fails to affect nvTRPM2 channel currents, reporting a catalytic cycle uncoupled from gating. Furthermore, pore sequence substitutions responsible for inactivation of hsTRPM2 also appeared in vertebrates. Correspondingly, zebrafish (Danio rerio) TRPM2 (drTRPM2) and hsTRPM2 channels inactivate, but srTRPM2 and nvTRPM2 currents are stable. Thus, catalysis and pore stability were lost simultaneously in vertebrate TRPM2 channels.
| Item Type: | Article |
|---|---|
| Subjects: | Q Science / természettudomány > Q1 Science (General) / természettudomány általában |
| Depositing User: | Balázs Tóth |
| Date Deposited: | 24 Sep 2019 14:45 |
| Last Modified: | 24 Sep 2019 14:45 |
| URI: | http://real.mtak.hu/id/eprint/101025 |
Available Versions of this Item
- Enzyme activity and selectivity filter stability of ancient TRPM2 channels were simultaneously lost in early vertebrates. (deposited 24 Sep 2019 14:45) [Currently Displayed]
Actions (login required)
 |
Edit Item |
