2la8 | pdb_00002la8
Solution structure of INAD PDZ5 complexed with Kon-tiki peptide
Structural highlights
Function[INAD_DROME] Involved in the negative feedback regulation of the light-activated signaling cascade in photoreceptors through a calcium-mediated process. Interacts with tetrapeptide ligand located in C-terminal sequence of 3 key components of the visual cascade, tethering them and forming a macromolecular signaling phototransduction complex.[1] [2] Publication Abstract from PubMedINAD is a scaffolding protein that regulates signaling in Drosophila photoreceptors. One of its PDZ domains, PDZ5, cycles between reduced and oxidized forms in response to light, but it is unclear how light affects its redox potential. Through biochemical and structural studies, we show that the redox potential of PDZ5 is allosterically regulated by its interaction with another INAD domain, PDZ4. Whereas isolated PDZ5 is stable in the oxidized state, formation of a PDZ45 "supramodule" locks PDZ5 in the reduced state by raising the redox potential of its Cys606/Cys645 disulfide bond by approximately 330 mV. Acidification, potentially mediated via light and PLCbeta-mediated hydrolysis of PIP(2), disrupts the interaction between PDZ4 and PDZ5, leading to PDZ5 oxidation and dissociation from the TRP Ca(2+) channel, a key component of fly visual signaling. These results show that scaffolding proteins can actively modulate the intrinsic redox potentials of their disulfide bonds to exert regulatory roles in signaling. The INAD scaffold is a dynamic, redox-regulated modulator of signaling in the Drosophila eye.,Liu W, Wen W, Wei Z, Yu J, Ye F, Liu CH, Hardie RC, Zhang M Cell. 2011 Jun 24;145(7):1088-101. PMID:21703451[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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