4qj3

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Structure of a fragment of human phospholipase C-beta3 delta472-559, in complex with Galphaq

Structural highlights

4qj3 is a 2 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.
Method:X-ray diffraction, Resolution 3Å
Ligands:ALF, CA, GDP, MG
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

Phospholipase C beta (PLCbeta) enzymes are dramatically activated by heterotrimeric G proteins. Central to this response is the robust autoinhibition of PLCbeta by the X-Y linker region within its catalytic core and by the Halpha2' helix in the C-terminal extension of the enzyme. The molecular mechanism of each and their mutual dependence are poorly understood. Herein, it is shown that distinct regions within the X-Y linker have specific roles in regulating activity. Most important, an acidic stretch within the linker stabilizes a lid that occludes the active site, consistent with crystal structures of variants lacking this region. Inhibition by the Halpha2' helix is independent of the X-Y linker and likely regulates activity by limiting membrane interaction of the catalytic core. Full activation of PLCbeta thus requires multiple independent molecular events induced by membrane association of the catalytic core and by the binding of regulatory proteins.

Molecular Mechanisms of Phospholipase C beta3 Autoinhibition.,Lyon AM, Begley JA, Manett TD, Tesmer JJ Structure. 2014 Nov 25. pii: S0969-2126(14)00335-9. doi:, 10.1016/j.str.2014.10.008. PMID:25435326[3]

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

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Citations
3 reviews cite this structure
Regulating G protein activity by lipase-independent functions of phospholipase C.
Litosch et al. (2015)
2 more
17 other articles
No citations found

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ Lyon AM, Begley JA, Manett TD, Tesmer JJ. Molecular Mechanisms of Phospholipase C beta3 Autoinhibition. Structure. 2014 Nov 25. pii: S0969-2126(14)00335-9. doi:, 10.1016/j.str.2014.10.008. PMID:25435326 doi:http://dx.doi.org/10.1016/j.str.2014.10.008

Contents


PDB ID 4qj3

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