An unexpected INAD PDZ tandem-mediated plcβ binding in <i>Drosophila</i> photo receptors.

Ye, Fei; Huang, Yuxin; Li, Jianchao; Ma, Yuqian; Xie, Chensu; Liu, Zexu; Deng, Xiaoying; Wan, Jun et al. · Elife · 2018

basic_science · Level V

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Abstract

INAD assembles key enzymes of the <i>Drosophila</i> compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. However, the molecular mechanism that governs the interaction between INAD and NORPA (phospholipase Cβ, PLCβ), a key step for the fast kinetics of the light signaling, is not known. Here, we show that the NORPA C-terminal coiled-coil domain and PDZ-binding motif (CC-PBM) synergistically bind to INAD PDZ45 tandem with an unexpected mode and unprecedented high affinity. Guided by the structure of the INAD-NORPA complex, we discover that INADL is probably a mammalian counterpart of INAD. The INADL PDZ89 tandem specifically binds to PLCβ4 with a mode that is strikingly similar to that of the INAD-NORPA complex, as revealed by the structure of the INADL PDZ89-PLCβ4 CC-PBM complex. Therefore, our study suggests that the highly specific PDZ tandem - PLCβ interactions are an evolutionarily conserved mechanism in PLCβ signaling in the animal kingdom.

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