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2b3r

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Revision as of 06:56, 16 May 2018

Crystal structure of the C2 domain of class II phosphatidylinositide 3-kinase C2

Structural highlights

2b3r is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	Pik3c2a, Cpk (LK3 transgenic mice)
Activity:	Phosphatidylinositol-4-phosphate 3-kinase, with EC number 2.7.1.154
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[P3C2A_MOUSE] Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain (MLC) phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function.^[1] ^[2] ^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Phosphatidylinositide (PtdIns) 3-kinase catalyzes the addition of a phosphate group to the 3'-position of phosphatidyl inositol. Accumulated evidence shows that PtdIns 3-kinase can provide a critical signal for cell proliferation, cell survival, membrane trafficking, glucose transport, and membrane ruffling. Mammalian PtdIns 3-kinases are divided into three classes based on structure and substrate specificity. A unique characteristic of class II PtdIns 3-kinases is the presence of both a phox homolog domain and a C2 domain at the C terminus. The biological function of the C2 domain of the class II PtdIns 3-kinases remains to be determined. We have determined the crystal structure of the mCPK-C2 domain, which is the first three-dimensional structural model of a C2 domain of class II PtdIns 3-kinases. Structural studies reveal that the mCPK-C2 domain has a typical anti-parallel beta-sandwich fold. Scrutiny of the surface of this C2 domain has identified three small, shallow sulfate-binding sites. On the basis of the structural features of these sulfate-binding sites, we have studied the lipid binding properties of the mCPK-C2 domain by site-directed mutagenesis. Our results show that this C2 domain binds specifically to PtdIns(3,4)P(2) and PtdIns(4,5)P(2) and that three lysine residues at SBS I site, Lys-1420, Lys-1432, and Lys-1434, are responsible for the phospholipid binding affinity.

Crystal structure of the C2 domain of class II phosphatidylinositide 3-kinase C2alpha.,Liu L, Song X, He D, Komma C, Kita A, Virbasius JV, Huang G, Bellamy HD, Miki K, Czech MP, Zhou GW J Biol Chem. 2006 Feb 17;281(7):4254-60. Epub 2005 Dec 7. PMID:16338929^[4]

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

References

↑ Virbasius JV, Guilherme A, Czech MP. Mouse p170 is a novel phosphatidylinositol 3-kinase containing a C2 domain. J Biol Chem. 1996 Jun 7;271(23):13304-7. PMID:8663140
↑ Leibiger B, Moede T, Uhles S, Barker CJ, Creveaux M, Domin J, Berggren PO, Leibiger IB. Insulin-feedback via PI3K-C2alpha activated PKBalpha/Akt1 is required for glucose-stimulated insulin secretion. FASEB J. 2010 Jun;24(6):1824-37. doi: 10.1096/fj.09-148072. Epub 2010 Jan 8. PMID:20061534 doi:http://dx.doi.org/10.1096/fj.09-148072
↑ Harris DP, Vogel P, Wims M, Moberg K, Humphries J, Jhaver KG, DaCosta CM, Shadoan MK, Xu N, Hansen GM, Balakrishnan S, Domin J, Powell DR, Oravecz T. Requirement for class II phosphoinositide 3-kinase C2alpha in maintenance of glomerular structure and function. Mol Cell Biol. 2011 Jan;31(1):63-80. doi: 10.1128/MCB.00468-10. Epub 2010 Oct 25. PMID:20974805 doi:http://dx.doi.org/10.1128/MCB.00468-10
↑ Liu L, Song X, He D, Komma C, Kita A, Virbasius JV, Huang G, Bellamy HD, Miki K, Czech MP, Zhou GW. Crystal structure of the C2 domain of class II phosphatidylinositide 3-kinase C2alpha. J Biol Chem. 2006 Feb 17;281(7):4254-60. Epub 2005 Dec 7. PMID:16338929 doi:10.1074/jbc.M510791200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2b3r"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the C2 domain of class II phosphatidylinositide 3-kinase C2==
 <StructureSection load='2b3r' size='340' side='right' caption='[[2b3r]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pik3c2a, Cpk ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphatidylinositol-4-phosphate_3-kinase Phosphatidylinositol-4-phosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.154 2.7.1.154] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2b3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b3r OCA], [http://pdbe.org/2b3r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2b3r RCSB], [http://www.ebi.ac.uk/pdbsum/2b3r PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2b3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b3r OCA], [http://pdbe.org/2b3r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2b3r RCSB], [http://www.ebi.ac.uk/pdbsum/2b3r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2b3r ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b3/2b3r_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b3/2b3r_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

2b3r

From Proteopedia

Revision as of 06:56, 16 May 2018

Crystal structure of the C2 domain of class II phosphatidylinositide 3-kinase C2

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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