6F55

Complex structure of PACSIN SH3 domain and TRPV4 proline rich region

Summary for 6F55

• Entry DOI: 10.2210/pdb6f55/pdb
• NMR Information: BMRB: 34211
• Descriptor: PACSIN 3, PRR (2 entities in total)
• Functional Keywords: protein, peptide binding protein
• Biological source: Gallus gallus (Chicken); More
• Total number of polymer chains: 2
• Total formula weight: 9015.33

Authors

Glogowski, N.A.,Goretzki, B.,Diehl, E.,Duchardt-Ferner, E.,Hacker, C.,Hellmich, U.A. (deposition date: 2017-11-30, release date: 2018-10-03, Last modification date: 2024-05-15)

Primary citation

Goretzki, B.,Glogowski, N.A.,Diehl, E.,Duchardt-Ferner, E.,Hacker, C.,Gaudet, R.,Hellmich, U.A.
Structural Basis of TRPV4 N Terminus Interaction with Syndapin/PACSIN1-3 and PIP2.
Structure, 26:1583-1593.e5, 2018

PubMed Abstract: Transient receptor potential (TRP) channels are polymodally regulated ion channels. TRPV4 (vanilloid 4) is sensitized by PIP 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 PIP binding site. We determined the affinities of the TRPV4 N terminus for PACSIN1, 2, and 3 SH3 domains and PIP and deduce a hierarchical interaction network where Syndapin/PACSIN binding influences the PIP binding site but not vice versa.

PubMed: 30244966
DOI: 10.1016/j.str.2018.08.002

Experimental method

SOLUTION NMR