View source for 6mhf


==Galphai3 co-crystallized with GIV/Girdin==
<StructureSection load='6mhf' size='340' side='right'caption='[[6mhf]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6mhf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MHF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MHF 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]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6mhf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mhf OCA], [https://pdbe.org/6mhf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mhf RCSB], [https://www.ebi.ac.uk/pdbsum/6mhf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mhf ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GRDN_HUMAN GRDN_HUMAN] PEHO-like syndrome. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/GRDN_HUMAN GRDN_HUMAN] Plays a role as a key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation (By similarity). Enhances phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase activity of AKT1/PKB, but does not possess kinase activity itself (By similarity). Phosphorylation of AKT1/PKB thereby induces the phosphorylation of downstream effectors GSK3 and FOXO1/FKHR, and regulates DNA replication and cell proliferation (By similarity). Essential for the integrity of the actin cytoskeleton and for cell migration (PubMed:16139227). Required for formation of actin stress fibers and lamellipodia (PubMed:15882442). May be involved in membrane sorting in the early endosome (PubMed:15882442). Plays a role in ciliogenesis and cilium morphology and positioning and this may partly be through regulation of the localization of scaffolding protein CROCC/Rootletin (PubMed:27623382).[UniProtKB:Q5SNZ0]<ref>PMID:15882442</ref> <ref>PMID:16139227</ref> <ref>PMID:27623382</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Heterotrimeric G proteins are key molecular switches that control cell behavior. The canonical activation of G proteins by agonist-occupied G protein-coupled receptors (GPCRs) has recently been elucidated from the structural perspective. In contrast, the structural basis for GPCR-independent G protein activation by a novel family of guanine-nucleotide exchange modulators (GEMs) remains unknown. Here, we present a 2.0-A crystal structure of Galphai in complex with the GEM motif of GIV/Girdin. Nucleotide exchange assays, molecular dynamics simulations, and hydrogen-deuterium exchange experiments demonstrate that GEM binding to the conformational switch II causes structural changes that allosterically propagate to the hydrophobic core of the Galphai GTPase domain. Rearrangement of the hydrophobic core appears to be a common mechanism by which GPCRs and GEMs activate G proteins, although with different efficiency. Atomic-level insights presented here will aid structure-based efforts to selectively target the noncanonical G protein activation.

Structural basis for GPCR-independent activation of heterotrimeric Gi proteins.,Kalogriopoulos NA, Rees SD, Ngo T, Kopcho NJ, Ilatovskiy AV, Sun N, Komives EA, Chang G, Ghosh P, Kufareva I Proc Natl Acad Sci U S A. 2019 Jul 30. pii: 1906658116. doi:, 10.1073/pnas.1906658116. PMID:31363053<ref>PMID:31363053</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6mhf" style="background-color:#fffaf0;"></div>

==See Also==
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Chang G]]
[[Category: Ghosh P]]
[[Category: Ilatovskiy A]]
[[Category: Kalogriopoulos NA]]
[[Category: Komives E]]
[[Category: Kopcho N]]
[[Category: Kufareva I]]
[[Category: Ngo T]]
[[Category: Rees SD]]
[[Category: Sun N]]