An unexpected INAD PDZ tandem-mediated PLCβ binding in Drosophila photo receptors
- Hong Kong University of Science and Technology, Hong Kong
- Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, China
- University of Science and Technology of China, China
Abstract
INAD assembles key enzymes of Drosophila compound eye photo-transduction pathway into a supramolecular complex, supporting efficient and fast light signaling. However, the molecular mechanism governing 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 unprecedentedly high affinity. Guided by the INAD/NORPA complex structure, we discover that INADL is likely a mammalian counterpart of INAD. The INADL PDZ89 tandem specifically binds to PLCβ4 with a strikingly similar mode 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 of the animal kingdom.
Data availability
Diffraction data have been deposited at PDB under the accession numbers 6IRB, 6IRC, 6IRD, and 6IRE.
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C-terminal domain of Drosophila phospholipase b NORPA, methylatedProtein Data Bank, 6IRC.
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Complex structure of INADL PDZ89 and PLCb4 C-terminal CC-PBMProtein Data Bank, 6IRD.
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Complex structure of INAD PDZ45 and NORPA CC-PBMProtein Data Bank, 6IRE.
Article and author information
Author details
Funding
Minister of Science and Technology of China (2014CB910204)
- Mingjie Zhang
Research Grant Council of Hong Kong (C6004-17)
- Mingjie Zhang
Shenzhen Basic Research Grant (JCYJ20170411090807530)
- Wei Liu
Shenzhen Basic Research Grant (JCYJ20160427185712266)
- Wei Liu
National Natural Science Foundation of China (31670765)
- Wei Liu
National Natural Science Foundation of China (31870746)
- Wei Liu
Chinese Academy of Sciences Key Project (XDPB10)
- Tian Xue
Chinese Academy of Sciences Key Project (XDB02010000)
- Tian Xue
Research Grant Council of Hong Kong (AoE-M09-12)
- Mingjie Zhang
National Key R&D Program of China (2016YFA0501903)
- Mingjie Zhang
Natural Science Foundation of Guangdong Province (2016A030312016)
- Mingjie Zhang
Shenzhen Basic Research Grant (JCYJ20160229153100269)
- Wei Liu
National Natural Science Foundation of China (81790644)
- Tian Xue
Chinese Academy of Sciences Key Project (XDA16020603)
- Tian Xue
National Key Basic Research Program of China (2016YFA0400900)
- Tian Xue
GRF grant from RGC of Hong Kong (16104518)
- Fei Ye
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Ye et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An unexpected INAD PDZ tandem-mediated PLCβ binding in Drosophila photo receptors
eLife 7:e41848.
https://doi.org/10.7554/eLife.41848
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