6oq3

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==Crystal Structure of the Ternary Complex of KRIT1 bound to both the Rap1 GTPase and HKi2==
==Crystal Structure of the Ternary Complex of KRIT1 bound to both the Rap1 GTPase and HKi2==
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<StructureSection load='6oq3' size='340' side='right'caption='[[6oq3]]' scene=''>
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<StructureSection load='6oq3' size='340' side='right'caption='[[6oq3]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OQ3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6OQ3 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6oq3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OQ3 FirstGlance]. <br>
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</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6oq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oq3 OCA], [http://pdbe.org/6oq3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6oq3 RCSB], [http://www.ebi.ac.uk/pdbsum/6oq3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6oq3 ProSAT]</span></td></tr>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7WO:2-HYDROXYNAPHTHALENE-1-CARBALDEHYDE'>7WO</scene>, <scene name='pdbligand=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[6oq4|6oq4]]</div></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KRIT1, CCM1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RAP1B, OK/SW-cl.11 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6oq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6oq3 OCA], [https://pdbe.org/6oq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6oq3 RCSB], [https://www.ebi.ac.uk/pdbsum/6oq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6oq3 ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
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[[https://www.uniprot.org/uniprot/KRIT1_HUMAN KRIT1_HUMAN]] Hereditary cerebral cavernous malformation. Cerebral cavernous malformations 1 (CCM1) [MIM:[https://omim.org/entry/116860 116860]]: A congenital vascular anomaly of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:12172908</ref>
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== Function ==
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[[https://www.uniprot.org/uniprot/KRIT1_HUMAN KRIT1_HUMAN]] Component of the CCM signaling pathway which is a crucial regulator of heart and vessel formation and integrity (By similarity). Negative regulator of angiogenesis. Inhibits endothelial proliferation, apoptosis, migration, lumen formation and sprouting angiogenesis in primary endothelial cells. Promotes AKT phosphorylation in a NOTCH-dependent and independent manner, and inhibits EKR1/2 phosphorylation indirectly through activation of the DELTA-NOTCH cascade. Acts in concert with CDH5 to establish and maintain correct endothelial cell polarity and vascular lumen and these effects are mediated by recruitment and activation of the Par polarity complex and RAP1B. Required for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction, and cell junction stabilization. Plays a role in integrin signaling via its interaction with ITGB1BP1; this prevents the interaction between ITGB1 and ITGB1BP1. Plays an important role in the maintenance of the intracellular reactive oxygen species (ROS) homeostasis to prevent oxidative cellular damage. Regulates the homeostasis of intracellular ROS through an antioxidant pathway involving FOXO1 and SOD2. Facilitates the down-regulation of cyclin-D1 (CCND1) levels required for cell transition from proliferative growth to quiescence by preventing the accumulation of intracellular ROS through the modulation of FOXO1 and SOD2 levels.<ref>PMID:20332120</ref> <ref>PMID:20668652</ref> <ref>PMID:20616044</ref> <ref>PMID:21633110</ref> [REFERENCE:17] [[https://www.uniprot.org/uniprot/RAP1B_HUMAN RAP1B_HUMAN]] GTP-binding protein that possesses intrinsic GTPase activity. Contributes to the polarizing activity of KRIT1 and CDH5 in the establishment and maintenance of correct endothelial cell polarity and vascular lumen. Required for the localization of phosphorylated PRKCZ, PARD3 and TIAM1 to the cell junction.<ref>PMID:20332120</ref> <ref>PMID:18660803</ref>
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==See Also==
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*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Gingras AR]]
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[[Category: Gingras, A R]]
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[[Category: Cell adhesion]]
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[[Category: Complex]]
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[[Category: Gtpase]]
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[[Category: Krit1]]
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[[Category: Small molecule]]

Revision as of 10:40, 31 March 2021

Crystal Structure of the Ternary Complex of KRIT1 bound to both the Rap1 GTPase and HKi2

PDB ID 6oq3

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