| Structural highlights
4gnk is a 5 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Gene: | g alpha q, Gnaq (Mus musculus), phospholipase c beta 3, PLCB3 (Homo sapiens) |
| Activity: | Phosphoinositide phospholipase C, with EC number 3.1.4.11 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[GNAQ_MOUSE] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro).[1] [2] [PLCB3_HUMAN] 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.
Publication Abstract from PubMed
Phospholipase C-beta (PLCbeta) is directly activated by Galphaq, but the molecular basis for how its distal C-terminal domain (CTD) contributes to maximal activity is poorly understood. Herein we present both the crystal structure and cryo-EM three-dimensional reconstructions of human full-length PLCbeta3 in complex with mouse Galphaq. The distal CTD forms an extended monomeric helical bundle consisting of three antiparallel segments with structural similarity to membrane-binding bin-amphiphysin-Rvs (BAR) domains. Sequence conservation of the distal CTD suggests putative membrane and protein interaction sites, the latter of which bind the N-terminal helix of Galphaq in both the crystal structure and cryo-EM reconstructions. Functional analysis suggests that the distal CTD has roles in membrane targeting and in optimizing the orientation of the catalytic core at the membrane for maximal rates of lipid hydrolysis.
Full-length Galpha(q)-phospholipase C-beta3 structure reveals interfaces of the C-terminal coiled-coil domain.,Lyon AM, Dutta S, Boguth CA, Skiniotis G, Tesmer JJ Nat Struct Mol Biol. 2013 Mar;20(3):355-62. doi: 10.1038/nsmb.2497. Epub 2013 Feb, 3. PMID:23377541[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shi G, Partida-Sanchez S, Misra RS, Tighe M, Borchers MT, Lee JJ, Simon MI, Lund FE. Identification of an alternative G{alpha}q-dependent chemokine receptor signal transduction pathway in dendritic cells and granulocytes. J Exp Med. 2007 Oct 29;204(11):2705-18. Epub 2007 Oct 15. PMID:17938235 doi:10.1084/jem.20071267
- ↑ Misra RS, Shi G, Moreno-Garcia ME, Thankappan A, Tighe M, Mousseau B, Kusser K, Becker-Herman S, Hudkins KL, Dunn R, Kehry MR, Migone TS, Marshak-Rothstein A, Simon M, Randall TD, Alpers CE, Liggitt D, Rawlings DJ, Lund FE. G alpha q-containing G proteins regulate B cell selection and survival and are required to prevent B cell-dependent autoimmunity. J Exp Med. 2010 Aug 2;207(8):1775-89. doi: 10.1084/jem.20092735. Epub 2010 Jul, 12. PMID:20624888 doi:10.1084/jem.20092735
- ↑ Lyon AM, Dutta S, Boguth CA, Skiniotis G, Tesmer JJ. Full-length Galpha(q)-phospholipase C-beta3 structure reveals interfaces of the C-terminal coiled-coil domain. Nat Struct Mol Biol. 2013 Mar;20(3):355-62. doi: 10.1038/nsmb.2497. Epub 2013 Feb, 3. PMID:23377541 doi:10.1038/nsmb.2497
|
