An unexpected INAD PDZ tandem-mediated plcβ binding in Drosophila photo receptors
INAD assembles key enzymes of the Drosophila 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 ki...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/41848 |
| _version_ | 1811202770966937600 |
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| author | Fei Ye Yuxin Huang Jianchao Li Yuqian Ma Chensu Xie Zexu Liu Xiaoying Deng Jun Wan Tian Xue Wei Liu Mingjie Zhang |
| author_facet | Fei Ye Yuxin Huang Jianchao Li Yuqian Ma Chensu Xie Zexu Liu Xiaoying Deng Jun Wan Tian Xue Wei Liu Mingjie Zhang |
| author_sort | Fei Ye |
| collection | DOAJ |
| description | INAD assembles key enzymes of the Drosophila 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. |
| first_indexed | 2024-04-12T02:44:17Z |
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| id | doaj.art-5fa428b201cd4c9ebae3efafe1ea2150 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:44:17Z |
| publishDate | 2018-12-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-5fa428b201cd4c9ebae3efafe1ea21502022-12-22T03:51:13ZengeLife Sciences Publications LtdeLife2050-084X2018-12-01710.7554/eLife.41848An unexpected INAD PDZ tandem-mediated plcβ binding in Drosophila photo receptorsFei Ye0https://orcid.org/0000-0002-4268-7256Yuxin Huang1Jianchao Li2https://orcid.org/0000-0002-8921-1626Yuqian Ma3Chensu Xie4Zexu Liu5Xiaoying Deng6Jun Wan7Tian Xue8Wei Liu9https://orcid.org/0000-0001-8250-2562Mingjie Zhang10https://orcid.org/0000-0001-9404-0190Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China; Institute for Advanced Study, Hong Kong University of Science and Technology, Hong Kong, ChinaShenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, ChinaDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, ChinaHefei National Laboratory for Physical Sciences at Microscale,CAS Key Laboratory of Brain Function and Disease, Neurodegenerative Disorder Research Center, School of Life Sciences, University of Science and Technology of China, Hefei, ChinaDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, ChinaDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, ChinaShenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, ChinaDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, ChinaHefei National Laboratory for Physical Sciences at Microscale,CAS Key Laboratory of Brain Function and Disease, Neurodegenerative Disorder Research Center, School of Life Sciences, University of Science and Technology of China, Hefei, ChinaShenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, ChinaDivision of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, China; Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, ChinaINAD assembles key enzymes of the Drosophila 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.https://elifesciences.org/articles/41848scaffold proteinsignal transductionprotein structurephotoreceptor transduction |
| spellingShingle | Fei Ye Yuxin Huang Jianchao Li Yuqian Ma Chensu Xie Zexu Liu Xiaoying Deng Jun Wan Tian Xue Wei Liu Mingjie Zhang An unexpected INAD PDZ tandem-mediated plcβ binding in Drosophila photo receptors eLife scaffold protein signal transduction protein structure photoreceptor transduction |
| title | An unexpected INAD PDZ tandem-mediated plcβ binding in Drosophila photo receptors |
| title_full | An unexpected INAD PDZ tandem-mediated plcβ binding in Drosophila photo receptors |
| title_fullStr | An unexpected INAD PDZ tandem-mediated plcβ binding in Drosophila photo receptors |
| title_full_unstemmed | An unexpected INAD PDZ tandem-mediated plcβ binding in Drosophila photo receptors |
| title_short | An unexpected INAD PDZ tandem-mediated plcβ binding in Drosophila photo receptors |
| title_sort | unexpected inad pdz tandem mediated plcβ binding in drosophila photo receptors |
| topic | scaffold protein signal transduction protein structure photoreceptor transduction |
| url | https://elifesciences.org/articles/41848 |
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