6irc

C-terminal domain of Drosophila phospholipase b NORPA, methylatedC-terminal domain of Drosophila phospholipase b NORPA, methylated

Structural highlights

6irc is a 1 chain structure with sequence from Drome. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:	norpA, PLC-beta, CG3620 (DROME)
Activity:	Phosphoinositide phospholipase C, with EC number 3.1.4.11
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PIPA_DROME] The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes (By similarity). Essential component of the phototransduction pathway (PubMed:2457447). Essential downstream component of a hh-signaling pathway which regulates the Duox-dependent gut immune response to bacterial uracil; required for the activation of Cad99C and consequently Cad99C-dependent endosome formation, which is essential for the Duox-dependent production of reactive oxygen species (ROS) in response to intestinal bacterial infection (PubMed:25639794).[UniProtKB:Q9P212]^[1] ^[2]

Publication Abstract from PubMed

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 Cbeta, PLCbeta), 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 PLCbeta4 with a mode that is strikingly similar to that of the INAD-NORPA complex, as revealed by the structure of the INADL PDZ89-PLCbeta4 CC-PBM complex. Therefore, our study suggests that the highly specific PDZ tandem - PLCbeta interactions are an evolutionarily conserved mechanism in PLCbeta signaling in the animal kingdom.

An unexpected INAD PDZ tandem-mediated plcbeta binding in Drosophila photo receptors.,Ye F, Huang Y, Li J, Ma Y, Xie C, Liu Z, Deng X, Wan J, Xue T, Liu W, Zhang M Elife. 2018 Dec 10;7. pii: 41848. doi: 10.7554/eLife.41848. PMID:30526850^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bloomquist BT, Shortridge RD, Schneuwly S, Perdew M, Montell C, Steller H, Rubin G, Pak WL. Isolation of a putative phospholipase C gene of Drosophila, norpA, and its role in phototransduction. Cell. 1988 Aug 26;54(5):723-33. PMID:2457447
↑ Lee KA, Kim B, Bhin J, Kim DH, You H, Kim EK, Kim SH, Ryu JH, Hwang D, Lee WJ. Bacterial uracil modulates Drosophila DUOX-dependent gut immunity via Hedgehog-induced signaling endosomes. Cell Host Microbe. 2015 Feb 11;17(2):191-204. doi: 10.1016/j.chom.2014.12.012., Epub 2015 Jan 29. PMID:25639794 doi:http://dx.doi.org/10.1016/j.chom.2014.12.012
↑ Ye F, Huang Y, Li J, Ma Y, Xie C, Liu Z, Deng X, Wan J, Xue T, Liu W, Zhang M. An unexpected INAD PDZ tandem-mediated plcbeta binding in Drosophila photo receptors. Elife. 2018 Dec 10;7. pii: 41848. doi: 10.7554/eLife.41848. PMID:30526850 doi:http://dx.doi.org/10.7554/eLife.41848

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OCA

[1] Bloomquist BT, Shortridge RD, Schneuwly S, Perdew M, Montell C, Steller H, Rubin G, Pak WL. Isolation of a putative phospholipase C gene of Drosophila, norpA, and its role in phototransduction. Cell. 1988 Aug 26;54(5):723-33. PMID:2457447

[2] Lee KA, Kim B, Bhin J, Kim DH, You H, Kim EK, Kim SH, Ryu JH, Hwang D, Lee WJ. Bacterial uracil modulates Drosophila DUOX-dependent gut immunity via Hedgehog-induced signaling endosomes. Cell Host Microbe. 2015 Feb 11;17(2):191-204. doi: 10.1016/j.chom.2014.12.012., Epub 2015 Jan 29. PMID:25639794 doi:http://dx.doi.org/10.1016/j.chom.2014.12.012

[3] Ye F, Huang Y, Li J, Ma Y, Xie C, Liu Z, Deng X, Wan J, Xue T, Liu W, Zhang M. An unexpected INAD PDZ tandem-mediated plcbeta binding in Drosophila photo receptors. Elife. 2018 Dec 10;7. pii: 41848. doi: 10.7554/eLife.41848. PMID:30526850 doi:http://dx.doi.org/10.7554/eLife.41848

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