4dx8

From Proteopedia

(Difference between revisions)

Revision as of 08:42, 21 September 2022

ICAP1 in complex with KRIT1 N-terminus

Structural highlights

4dx8 is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ITBP1_HUMAN] Regulates integrin signaling by binding to the ITGB1 cytoplasmic tail and preventing the activation of integrin alpha-5/beta-1 (heterodimer of ITGA5 and ITGB1) by talin or FERMT1. May play a role in the recruitment of ITGB1 to focal contacts during integrin-dependent cell adhesion.[REFERENCE:8]

Publication Abstract from PubMed

KRIT1 (Krev/Rap1 Interaction Trapped-1) mutations are observed in approximately 40% of autosomal-dominant cerebral cavernous malformations (CCMs), a disease occurring in up to 0.5% of the population. We show that KRIT1 functions as a switch for beta1 integrin activation by antagonizing ICAP1 (Integrin Cytoplasmic Associated Protein-1)-mediated modulation of "inside-out" activation. We present cocrystal structures of KRIT1 with ICAP1 and ICAP1 with integrin beta1 cytoplasmic tail to 2.54 and 3.0 A resolution (the resolutions at which I/sigmaI = 2 are 2.75 and 3.0 A, respectively). We find that KRIT1 binds ICAP1 by a bidentate surface, that KRIT1 directly competes with integrin beta1 to bind ICAP1, and that KRIT1 antagonizes ICAP1-modulated integrin activation using this site. We also find that KRIT1 contains an N-terminal Nudix domain, in a region previously designated as unstructured. We therefore provide insights to integrin regulation and CCM-associated KRIT1 function.

Mechanism for KRIT1 Release of ICAP1-Mediated Suppression of Integrin Activation.,Liu W, Draheim KM, Zhang R, Calderwood DA, Boggon TJ Mol Cell. 2013 Jan 9. pii: S1097-2765(12)01014-3. doi:, 10.1016/j.molcel.2012.12.005. PMID:23317506^[1]

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

References

↑ Liu W, Draheim KM, Zhang R, Calderwood DA, Boggon TJ. Mechanism for KRIT1 Release of ICAP1-Mediated Suppression of Integrin Activation. Mol Cell. 2013 Jan 9. pii: S1097-2765(12)01014-3. doi:, 10.1016/j.molcel.2012.12.005. PMID:23317506 doi:http://dx.doi.org/10.1016/j.molcel.2012.12.005

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4dx8"

@@ Line 3: / Line 3: @@
 <StructureSection load='4dx8' size='340' side='right'caption='[[4dx8]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4dx8]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DX8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4DX8 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4dx8]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DX8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DX8 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dx9|4dx9]], [[4dxa|4dxa]]</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=4dx8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dx8 OCA], [https://pdbe.org/4dx8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dx8 RCSB], [https://www.ebi.ac.uk/pdbsum/4dx8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dx8 ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ICAP1, Integrin cytoplasmic domain-associated protein 1 (ICAP1), ITGB1BP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCM1, Krev interaction trapped protein 1 (KRIT1), KRIT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4dx8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dx8 OCA], [http://pdbe.org/4dx8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dx8 RCSB], [http://www.ebi.ac.uk/pdbsum/4dx8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dx8 ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/KRIT1_HUMAN KRIT1_HUMAN]] Hereditary cerebral cavernous malformation. Cerebral cavernous malformations 1 (CCM1) [MIM:[http://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>
 == Function ==
-[[http://www.uniprot.org/uniprot/ITBP1_HUMAN ITBP1_HUMAN]] Regulates integrin signaling by binding to the ITGB1 cytoplasmic tail and preventing the activation of integrin alpha-5/beta-1 (heterodimer of ITGA5 and ITGB1) by talin or FERMT1. May play a role in the recruitment of ITGB1 to focal contacts during integrin-dependent cell adhesion.[REFERENCE:8] [[http://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/ITBP1_HUMAN ITBP1_HUMAN]] Regulates integrin signaling by binding to the ITGB1 cytoplasmic tail and preventing the activation of integrin alpha-5/beta-1 (heterodimer of ITGA5 and ITGB1) by talin or FERMT1. May play a role in the recruitment of ITGB1 to focal contacts during integrin-dependent cell adhesion.[REFERENCE:8]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Boggon, T J]]
+[[Category: Boggon TJ]]
-[[Category: Calderwood, D A]]
+[[Category: Calderwood DA]]
-[[Category: Draheim, K]]
+[[Category: Draheim K]]
-[[Category: Liu, W]]
+[[Category: Liu W]]
-[[Category: Zhang, R]]
+[[Category: Zhang R]]
-[[Category: Membrane]]
-[[Category: Nucleus]]
-[[Category: Nudix fold]]
-[[Category: Protein binding]]
-[[Category: Protein-protein complex]]
-[[Category: Protein-protein interaction]]
-[[Category: Ptb domain]]

4dx8

From Proteopedia

Revision as of 08:42, 21 September 2022

ICAP1 in complex with KRIT1 N-terminus

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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