Journal
STRUCTURE
Volume 26, Issue 12, Pages 1583-+Publisher
CELL PRESS
DOI: 10.1016/j.str.2018.08.002
Keywords
-
Funding
- Max Planck Graduate Center (MPGC)
- Boehringer Ingelheim
- TransMED-Mainz Research School of Translational Biomedicine
- NIH [R01 GM081340]
- Carl Zeiss Foundation
- Naturwissenschaftlich-Medizinisches Forschungszentrum (NMFZ), Mainz University
- Naturwissenschaftlich-Medizinisches Forschungszentrum (NMFZ), University Medicine Mainz
- Center of Biomolecular Magnetic Resonance (BMRZ) - state of Hesse
Ask authors/readers for more resources
Transient receptor potential (TRP) channels are poly-modally regulated ion channels. TRPV4 (vanilloid 4) is sensitized by PIP2 and desensitized by Syndapin3/PACSIN3, which bind to the structurally uncharacterized TRPV4 N terminus. We determined the nuclear magnetic resonance structure of the Syndapin3/PACSIN3 SH3 domain in complex with the TRPV4 N-terminal proline-rich region (PRR), which binds as a class I polyproline II (PPII) helix. This PPII conformation is broken by a conserved proline in a cis conformation. Beyond the PPII, we find that the proximal TRPV4 N terminus is unstructured, a feature conserved across species thus explaining the difficulties in resolving it in previous structural studies. Syndapin/PACSIN SH3 domain binding leads to rigidification of both the PRR and the adjacent PIP2 binding site. We determined the affinities of the TRPV4 N terminus for PACSIN1, 2, and 3 SH3 domains and PIP2 and deduce a hierarchical interaction network where Syndapin/PACSIN binding influences the PIP2 binding site but not vice versa.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available