Structural Investigations of Human TRPM4
EMSL Project ID
51237
Abstract
The aim of this research is to complete the gating cycle of human TRPM4by solving the structures at multiple functional states at high-resolution. The recently published TRPM4
structures by our lab and other labs reveal the unique architecture of a TRPM family member, including
the binding sites of the agonist calcium, the allosteric modulator DVT and the inhibitor ATP. However, all
these structures show a similar configuration, that is, a closed pore, with vague definition of the functional
state. In this long-term proposal, we aim to solve a bona fide open state of TRPM4 by utilizing multiple
approaches including mutagenesis, positive modulators or SMA; we also aim to determine the structures
of TRPM4 in complex with several available modulators such as negative modulator P9O. Achieving the
goals in this proposal will allow us to understand relationships between structure and function for the
TRPM4 channel.
Project Details
Start Date
2020-01-15
End Date
2021-03-17
Status
Closed
Released Data Link
Team
Principal Investigator
Co-Investigator(s)
Team Members