7bi9

From Proteopedia

(Difference between revisions)

Current revision

PI3KC2a core in complex with PIK90

Structural highlights

7bi9 is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.65Å
Ligands:	,
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]

Publication Abstract from PubMed

Phosphatidylinositol 3-kinase type 2alpha (PI3KC2alpha) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2alpha is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-A cryogenic-electron microscopic (cryo-EM) structure of PI3KC2alpha in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2alpha at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2alpha-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine.

Structural basis of phosphatidylinositol 3-kinase C2alpha function.,Lo WT, Zhang Y, Vadas O, Roske Y, Gulluni F, De Santis MC, Zagar AV, Stephanowitz H, Hirsch E, Liu F, Daumke O, Kudryashev M, Haucke V Nat Struct Mol Biol. 2022 Mar;29(3):218-228. doi: 10.1038/s41594-022-00730-w., Epub 2022 Mar 7. PMID:35256802^[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
↑ Lo WT, Zhang Y, Vadas O, Roske Y, Gulluni F, De Santis MC, Zagar AV, Stephanowitz H, Hirsch E, Liu F, Daumke O, Kudryashev M, Haucke V. Structural basis of phosphatidylinositol 3-kinase C2alpha function. Nat Struct Mol Biol. 2022 Mar;29(3):218-228. doi: 10.1038/s41594-022-00730-w., Epub 2022 Mar 7. PMID:35256802 doi:http://dx.doi.org/10.1038/s41594-022-00730-w

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7bi9"

@@ Line 3: / Line 3: @@
 <StructureSection load='7bi9' size='340' side='right'caption='[[7bi9]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7bi9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BI9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7bi9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BI9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BI9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=090:N-(2,3-DIHYDRO-7,8-DIMETHOXYIMIDAZO[1,2-C]+QUINAZOLIN-5-YL)NICOTINAMIDE'>090</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=090:N-(2,3-DIHYDRO-7,8-DIMETHOXYIMIDAZO[1,2-C]+QUINAZOLIN-5-YL)NICOTINAMIDE'>090</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7bi9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bi9 OCA], [https://pdbe.org/7bi9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bi9 RCSB], [https://www.ebi.ac.uk/pdbsum/7bi9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bi9 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/P3C2A_MOUSE 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.<ref>PMID:8663140</ref> <ref>PMID:20061534</ref> <ref>PMID:20974805</ref>
+[https://www.uniprot.org/uniprot/P3C2A_MOUSE 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.<ref>PMID:8663140</ref> <ref>PMID:20061534</ref> <ref>PMID:20974805</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 7bi9" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Phosphoinositide 3-kinase 3D structures|Phosphoinositide 3-kinase 3D structures]]
 == References ==
 <references/>
@@ Line 23: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Daumke, O]]
+[[Category: Mus musculus]]
-[[Category: Haucke, V]]
+[[Category: Daumke O]]
-[[Category: Lo, W T]]
+[[Category: Haucke V]]
-[[Category: Roske, Y]]
+[[Category: Lo WT]]
-[[Category: Kinase]]
+[[Category: Roske Y]]
-[[Category: Pi3kc2 alpha]]
-[[Category: Transferase]]

7bi9

From Proteopedia

Current revision

PI3KC2a core in complex with PIK90

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox