3R0H

Structure of INAD PDZ45 in complex with NG2 peptide

Summary for 3R0H

• Entry DOI: 10.2210/pdb3r0h/pdb
• Related: 2LA8
• Descriptor: Inactivation-no-after-potential D protein, NG2, 2,3-DIHYDROXY-1,4-DITHIOBUTANE, ... (6 entities in total)
• Functional Keywords: protein-protein complex, pdz domain, peptide binding protein
• Biological source: Drosophila melanogaster (Fruit fly); More
• Cellular location: Cell membrane; Peripheral membrane protein: Q24008
• Total number of polymer chains: 16
• Total formula weight: 190166.90

Authors

Wei, Z.,Liu, W.,Zhang, M. (deposition date: 2011-03-08, release date: 2011-11-30, Last modification date: 2024-03-20)

Primary citation

Liu, W.,Wen, W.,Wei, Z.,Yu, J.,Ye, F.,Liu, C.-H.,Hardie, R.C.,Zhang, M.
The INAD scaffold is a dynamic, redox-regulated modulator of signaling in the Drosophila eye
Cell(Cambridge,Mass.), 145:1088-1101, 2011

PubMed Abstract: INAD 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 ∼330 mV. Acidification, potentially mediated via light and PLCβ-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.

PubMed: 21703451
DOI: 10.1016/j.cell.2011.05.015

Experimental method

X-RAY DIFFRACTION (2.6 Å)