6qdt

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "6qdt" [edit=sysop:move=sysop])
Current revision (13:02, 6 November 2024) (edit) (undo)
 
(3 intermediate revisions not shown.)
Line 1: Line 1:
-
'''Unreleased structure'''
 
-
The entry 6qdt is ON HOLD until Paper Publication
+
==Crystal structure of 14-3-3sigma in complex with a RapGef2 pT740 phosphopeptide==
 +
<StructureSection load='6qdt' size='340' side='right'caption='[[6qdt]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[6qdt]] is a 2 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=6QDT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QDT FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.702&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=6qdt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qdt OCA], [https://pdbe.org/6qdt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qdt RCSB], [https://www.ebi.ac.uk/pdbsum/6qdt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qdt ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/RPGF2_HUMAN RPGF2_HUMAN] The disease is caused by mutations affecting the gene represented in this entry.
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/RPGF2_HUMAN RPGF2_HUMAN] Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Acts also as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10608844, PubMed:10548487, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Provides also inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions.<ref>PMID:10548487</ref> <ref>PMID:10608844</ref> <ref>PMID:10608883</ref> <ref>PMID:10801446</ref> <ref>PMID:10934204</ref> <ref>PMID:11359771</ref> <ref>PMID:12391161</ref> <ref>PMID:16272156</ref> <ref>PMID:17724123</ref> <ref>PMID:21840392</ref> <ref>PMID:23800469</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Targeting protein-protein interactions (PPIs) is a promising approach in the development of drugs for many indications. 14-3-3 proteins are a family of phosphoprotein-binding molecules with critical functions in dozens of cell signaling networks. 14-3-3s are abundant in the central nervous system, and the small molecule fusicoccin-A (FC-A), a tool compound that can be used to manipulate 14-3-3 PPIs, enhances neurite outgrowth in cultured neurons. New semisynthetic FC-A derivatives with improved binding affinity for 14-3-3 complexes have recently been developed. Here, we use a series of screens that identify these compounds as potent inducers of neurite outgrowth through a polypharmacological mechanism. Using proteomics and X-ray crystallography, we discover that these compounds extensively regulate the 14-3-3 interactome by stabilizing specific PPIs, while disrupting others. These results provide new insights into the development of drugs to target 14-3-3 PPIs, a potential therapeutic strategy for CNS diseases.
-
Authors:
+
Polypharmacological Perturbation of the 14-3-3 Adaptor Protein Interactome Stimulates Neurite Outgrowth.,Kaplan A, Andrei SA, van Regteren Altena A, Simas T, Banerjee SL, Kato N, Bisson N, Higuchi Y, Ottmann C, Fournier AE Cell Chem Biol. 2020 Jun 18;27(6):657-667.e6. doi:, 10.1016/j.chembiol.2020.02.010. Epub 2020 Mar 26. PMID:32220335<ref>PMID:32220335</ref>
-
Description:
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[Category: Unreleased Structures]]
+
</div>
 +
<div class="pdbe-citations 6qdt" style="background-color:#fffaf0;"></div>
 +
 
 +
==See Also==
 +
*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Homo sapiens]]
 +
[[Category: Large Structures]]
 +
[[Category: Andrei SA]]
 +
[[Category: Fournier AE]]
 +
[[Category: Kaplan A]]
 +
[[Category: Ottman C]]

Current revision

Crystal structure of 14-3-3sigma in complex with a RapGef2 pT740 phosphopeptide

PDB ID 6qdt

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6qdt"
Personal tools