Download MendeleyDynamic Scaffolding in a G Protein-Coupled Signaling System.
Mishra, P., Socolich, M., Wall, M.A., Graves, J., Wang, Z., Ranganathan, R.(2007) Cell 131: 80-92
- PubMed: 17923089
- DOI: https://doi.org/10.1016/j.cell.2007.07.037
- Primary Citation of Related Structures:
2QKT, 2QKU, 2QKV - PubMed Abstract:
The INAD scaffold organizes a multiprotein complex that is essential for proper visual signaling in Drosophila photoreceptor cells. Here we show that one of the INAD PDZ domains (PDZ5) exists in a redox-dependent equilibrium between two conformations--a reduced form that is similar to the structure of other PDZ domains, and an oxidized form in which the ligand-binding site is distorted through formation of a strong intramolecular disulfide bond. We demonstrate transient light-dependent formation of this disulfide bond in vivo and find that transgenic flies expressing a mutant INAD in which PDZ5 is locked in the reduced state display severe defects in termination of visual responses and visually mediated reflex behavior. These studies demonstrate a conformational switch mechanism for PDZ domain function and suggest that INAD behaves more like a dynamic machine rather than a passive scaffold, regulating signal transduction at the millisecond timescale through cycles of conformational change.
Organizational Affiliation:
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9050, USA.
