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| | ==Triglycine variant of the Grp1 Pleckstrin Homology Domain unliganded== | | ==Triglycine variant of the Grp1 Pleckstrin Homology Domain unliganded== |
| - | <StructureSection load='1u2b' size='340' side='right' caption='[[1u2b]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='1u2b' size='340' side='right'caption='[[1u2b]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1u2b]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U2B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1U2B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1u2b]] 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=1U2B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U2B FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1u27|1u27]], [[1u29|1u29]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pscd3, Grp1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=1u2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u2b OCA], [https://pdbe.org/1u2b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u2b RCSB], [https://www.ebi.ac.uk/pdbsum/1u2b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u2b ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1u2b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u2b OCA], [http://pdbe.org/1u2b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u2b RCSB], [http://www.ebi.ac.uk/pdbsum/1u2b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1u2b ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CYH3_MOUSE CYH3_MOUSE]] Promotes guanine-nucleotide exchange on ARF1. Promotes the activation of ARF factors through replacement of GDP with GTP.<ref>PMID:18042453</ref> | + | [https://www.uniprot.org/uniprot/CYH3_MOUSE CYH3_MOUSE] Promotes guanine-nucleotide exchange on ARF1. Promotes the activation of ARF factors through replacement of GDP with GTP.<ref>PMID:18042453</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Cronin, T C]] | + | [[Category: Mus musculus]] |
| - | [[Category: Czech, M P]] | + | [[Category: Cronin TC]] |
| - | [[Category: DiNitto, J P]] | + | [[Category: Czech MP]] |
| - | [[Category: Lambright, D G]] | + | [[Category: DiNitto JP]] |
| - | [[Category: Lipid binding]] | + | [[Category: Lambright DG]] |
| - | [[Category: Lipid binding protein]]
| + | |
| - | [[Category: Ph domain]]
| + | |
| - | [[Category: Phosphoinositide]]
| + | |
| Structural highlights
Function
CYH3_MOUSE Promotes guanine-nucleotide exchange on ARF1. Promotes the activation of ARF factors through replacement of GDP with GTP.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The pleckstrin homology (PH) domains of the homologous proteins Grp1 (general receptor for phosphoinositides), ARNO (Arf nucleotide binding site opener), and Cytohesin-1 bind phosphatidylinositol (PtdIns) 3,4,5-trisphosphate with unusually high selectivity. Remarkably, splice variants that differ only by the insertion of a single glycine residue in the beta1/beta2 loop exhibit dual specificity for PtdIns(3,4,5)P(3) and PtdIns(4,5)P(2). The structural basis for this dramatic specificity switch is not apparent from the known modes of phosphoinositide recognition. Here, we report crystal structures for dual specificity variants of the Grp1 and ARNO PH domains in either the unliganded form or in complex with the head groups of PtdIns(4,5)P(2) and PtdIns(3,4,5)P(3). Loss of contacts with the beta1/beta2 loop with no significant change in head group orientation accounts for the significant decrease in PtdIns(3,4,5)P(3) affinity observed for the dual specificity variants. Conversely, a small increase rather than decrease in affinity for PtdIns(4,5)P(2) is explained by a novel binding mode, in which the glycine insertion alleviates unfavorable interactions with the beta1/beta2 loop. These observations are supported by a systematic mutational analysis of the determinants of phosphoinositide recognition.
Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains.,Cronin TC, DiNitto JP, Czech MP, Lambright DG EMBO J. 2004 Oct 1;23(19):3711-20. Epub 2004 Sep 9. PMID:15359279[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ DiNitto JP, Delprato A, Gabe Lee MT, Cronin TC, Huang S, Guilherme A, Czech MP, Lambright DG. Structural basis and mechanism of autoregulation in 3-phosphoinositide-dependent Grp1 family Arf GTPase exchange factors. Mol Cell. 2007 Nov 30;28(4):569-83. PMID:18042453 doi:10.1016/j.molcel.2007.09.017
- ↑ Cronin TC, DiNitto JP, Czech MP, Lambright DG. Structural determinants of phosphoinositide selectivity in splice variants of Grp1 family PH domains. EMBO J. 2004 Oct 1;23(19):3711-20. Epub 2004 Sep 9. PMID:15359279 doi:10.1038/sj.emboj.7600388
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