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| | ==Solution structure of rat Kalirin N-terminal SH3 domain== | | ==Solution structure of rat Kalirin N-terminal SH3 domain== |
| - | <StructureSection load='1u3o' size='340' side='right' caption='[[1u3o]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1u3o' size='340' side='right'caption='[[1u3o]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1u3o]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U3O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1U3O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1u3o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U3O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U3O FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Kalirin, HAPIP, Duo ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1u3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u3o OCA], [http://pdbe.org/1u3o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1u3o RCSB], [http://www.ebi.ac.uk/pdbsum/1u3o PDBsum]</span></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=1u3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u3o OCA], [https://pdbe.org/1u3o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u3o RCSB], [https://www.ebi.ac.uk/pdbsum/1u3o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u3o ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/KALRN_RAT KALRN_RAT] Promotes the exchange of GDP by GTP. Activates specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulate neuronal shape, growth, and plasticity, through their effects on the actin cytoskeleton. Induces lamellipodia independent of its GEF activity. Isoforms 1 and 7 are necessary for neuronal development and axonal outgrowth. Isoform 6 is required for dendritic spine formation.<ref>PMID:10692441</ref> <ref>PMID:11606631</ref> <ref>PMID:15950621</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u3/1u3o_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u3/1u3o_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Chakrabarti, K]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Eipper, B A]] | + | [[Category: Chakrabarti K]] |
| - | [[Category: King, G F]] | + | [[Category: Eipper BA]] |
| - | [[Category: Maciejewski, M W]] | + | [[Category: King GF]] |
| - | [[Category: Schiller, M R]] | + | [[Category: Maciejewski MW]] |
| - | [[Category: Schiller, N I]] | + | [[Category: Schiller MR]] |
| - | [[Category: Cis-proline]] | + | [[Category: Schiller NI]] |
| - | [[Category: Sh3]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
KALRN_RAT Promotes the exchange of GDP by GTP. Activates specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulate neuronal shape, growth, and plasticity, through their effects on the actin cytoskeleton. Induces lamellipodia independent of its GEF activity. Isoforms 1 and 7 are necessary for neuronal development and axonal outgrowth. Isoform 6 is required for dendritic spine formation.[1] [2] [3]
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
RhoGEFs are central controllers of small G-proteins in cells and are regulated by several mechanisms. There are at least 22 human RhoGEFs that contain SH3 domains, raising the possibility that, like several other enzymes, SH3 domains control the enzymatic activity of guanine nucleotide exchange factor (GEF) domains through intra- and/or intermolecular interactions. The structure of the N-terminal SH3 domain of Kalirin was solved using NMR spectroscopy, and it folds much like other SH3 domains. However, NMR chemical shift mapping experiments showed that this Kalirin SH3 domain is unique, containing novel cooperative binding site(s) for intramolecular PXXP ligands. Intramolecular Kalirin SH3 domain/ligand interactions, as well as binding of the Kalirin SH3 domain to the adaptor protein Crk, inhibit the GEF activity of Kalirin. This study establishes a novel molecular mechanism whereby intramolecular and intermolecular Kalirin SH3 domain/ligand interactions modulate GEF activity, a regulatory mechanism that is likely used by other RhoGEF family members.
Regulation of RhoGEF activity by intramolecular and intermolecular SH3 domain interactions.,Schiller MR, Chakrabarti K, King GF, Schiller NI, Eipper BA, Maciejewski MW J Biol Chem. 2006 Jul 7;281(27):18774-86. Epub 2006 Apr 27. PMID:16644733[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Penzes P, Johnson RC, Alam MR, Kambampati V, Mains RE, Eipper BA. An isoform of kalirin, a brain-specific GDP/GTP exchange factor, is enriched in the postsynaptic density fraction. J Biol Chem. 2000 Mar 3;275(9):6395-403. PMID:10692441
- ↑ Penzes P, Johnson RC, Kambampati V, Mains RE, Eipper BA. Distinct roles for the two Rho GDP/GTP exchange factor domains of kalirin in regulation of neurite growth and neuronal morphology. J Neurosci. 2001 Nov 1;21(21):8426-34. PMID:11606631
- ↑ Schiller MR, Blangy A, Huang J, Mains RE, Eipper BA. Induction of lamellipodia by Kalirin does not require its guanine nucleotide exchange factor activity. Exp Cell Res. 2005 Jul 15;307(2):402-17. Epub 2005 Apr 21. PMID:15950621 doi:http://dx.doi.org/10.1016/j.yexcr.2005.03.024
- ↑ Schiller MR, Chakrabarti K, King GF, Schiller NI, Eipper BA, Maciejewski MW. Regulation of RhoGEF activity by intramolecular and intermolecular SH3 domain interactions. J Biol Chem. 2006 Jul 7;281(27):18774-86. Epub 2006 Apr 27. PMID:16644733 doi:10.1074/jbc.M512482200
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