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| | ==Structure of LGN GL4/Galphai3(Q147L) complex== | | ==Structure of LGN GL4/Galphai3(Q147L) complex== |
| - | <StructureSection load='4g5o' size='340' side='right' caption='[[4g5o]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='4g5o' size='340' side='right'caption='[[4g5o]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4g5o]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G5O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G5O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4g5o]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G5O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G5O FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <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]] 2.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4g5q|4g5q]], [[4g5r|4g5r]], [[4g5s|4g5s]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GNAI3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=4g5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g5o OCA], [https://pdbe.org/4g5o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g5o RCSB], [https://www.ebi.ac.uk/pdbsum/4g5o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g5o 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=4g5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g5o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4g5o RCSB], [http://www.ebi.ac.uk/pdbsum/4g5o PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/GNAI3_HUMAN GNAI3_HUMAN]] Defects in GNAI3 are the cause of auriculocondylar syndrome 1 (ARCND1) [MIM:[http://omim.org/entry/602483 602483]]. ARCND1 is an autosomal dominant craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia.<ref>PMID:22560091</ref> | + | [https://www.uniprot.org/uniprot/GNAI3_HUMAN GNAI3_HUMAN] Defects in GNAI3 are the cause of auriculocondylar syndrome 1 (ARCND1) [MIM:[https://omim.org/entry/602483 602483]. ARCND1 is an autosomal dominant craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia.<ref>PMID:22560091</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GNAI3_HUMAN GNAI3_HUMAN]] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. G(k) is the stimulatory G protein of receptor-regulated K(+) channels. The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> [[http://www.uniprot.org/uniprot/GPSM2_MOUSE GPSM2_MOUSE]] Plays an important role in spindle pole orientation (By similarity). Interacts and contributes to the functional activity of G(i) alpha proteins. Acts to stabilize the apical complex during neuroblast divisions. | + | [https://www.uniprot.org/uniprot/GNAI3_HUMAN GNAI3_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. G(k) is the stimulatory G protein of receptor-regulated K(+) channels. The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | GoLoco (GL) motif-containing proteins regulate G protein signaling by binding to Galpha subunit and acting as guanine nucleotide dissociation inhibitors. GLs of LGN are also known to bind the GDP form of Galpha(i/o) during asymmetric cell division. Here, we show that the C-terminal GL domain of LGN binds four molecules of Galpha(i).GDP. The crystal structures of Galpha(i).GDP in complex with LGN GL3 and GL4, respectively, reveal distinct GL/Galpha(i) interaction features when compared with the only high resolution structure known with GL/Galpha(i) interaction between RGS14 and Galpha(i1.) Only a few residues C-terminal to the conserved GL sequence are required for LGN GLs to bind to Galpha(i).GDP. A highly conserved "double Arg finger" sequence (RPsi(D/E)(D/E)QR) is responsible for LGN GL to bind to GDP bound to Galpha(i). Together with the sequence alignment, we suggest that the LGN GL/Galpha(i) interaction represents a general binding mode between GL motifs and Galpha(i). We also show that LGN GLs are potent guanine nucleotide dissociation inhibitors. |
| | + | |
| | + | Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Galphai.,Jia M, Li J, Zhu J, Wen W, Zhang M, Wang W J Biol Chem. 2012 Oct 26;287(44):36766-76. doi: 10.1074/jbc.M112.391607. Epub , 2012 Sep 5. PMID:22952234<ref>PMID:22952234</ref> |
| | | | |
| - | ==See Also== | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | *[[Guanine nucleotide-binding protein|Guanine nucleotide-binding protein]]
| + | </div> |
| | + | <div class="pdbe-citations 4g5o" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Jia, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, J]] | + | [[Category: Mus musculus]] |
| - | [[Category: Wang, W]] | + | [[Category: Jia M]] |
| - | [[Category: Wen, W]]
| + | [[Category: Li J]] |
| - | [[Category: Zhang, M]]
| + | [[Category: Wang W]] |
| - | [[Category: Zhu, J]] | + | [[Category: Wen W]] |
| - | [[Category: Asymmetric cell division]] | + | [[Category: Zhang M]] |
| - | [[Category: Cell cycle-signaling protein complex]] | + | [[Category: Zhu J]] |
| - | [[Category: Galpha signaling]] | + | |
| - | [[Category: Galphai]] | + | |
| - | [[Category: Goloco]]
| + | |
| Structural highlights
Disease
GNAI3_HUMAN Defects in GNAI3 are the cause of auriculocondylar syndrome 1 (ARCND1) [MIM:602483. ARCND1 is an autosomal dominant craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia.[1]
Function
GNAI3_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. G(k) is the stimulatory G protein of receptor-regulated K(+) channels. The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.[2]
Publication Abstract from PubMed
GoLoco (GL) motif-containing proteins regulate G protein signaling by binding to Galpha subunit and acting as guanine nucleotide dissociation inhibitors. GLs of LGN are also known to bind the GDP form of Galpha(i/o) during asymmetric cell division. Here, we show that the C-terminal GL domain of LGN binds four molecules of Galpha(i).GDP. The crystal structures of Galpha(i).GDP in complex with LGN GL3 and GL4, respectively, reveal distinct GL/Galpha(i) interaction features when compared with the only high resolution structure known with GL/Galpha(i) interaction between RGS14 and Galpha(i1.) Only a few residues C-terminal to the conserved GL sequence are required for LGN GLs to bind to Galpha(i).GDP. A highly conserved "double Arg finger" sequence (RPsi(D/E)(D/E)QR) is responsible for LGN GL to bind to GDP bound to Galpha(i). Together with the sequence alignment, we suggest that the LGN GL/Galpha(i) interaction represents a general binding mode between GL motifs and Galpha(i). We also show that LGN GLs are potent guanine nucleotide dissociation inhibitors.
Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Galphai.,Jia M, Li J, Zhu J, Wen W, Zhang M, Wang W J Biol Chem. 2012 Oct 26;287(44):36766-76. doi: 10.1074/jbc.M112.391607. Epub , 2012 Sep 5. PMID:22952234[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rieder MJ, Green GE, Park SS, Stamper BD, Gordon CT, Johnson JM, Cunniff CM, Smith JD, Emery SB, Lyonnet S, Amiel J, Holder M, Heggie AA, Bamshad MJ, Nickerson DA, Cox TC, Hing AV, Horst JA, Cunningham ML. A human homeotic transformation resulting from mutations in PLCB4 and GNAI3 causes auriculocondylar syndrome. Am J Hum Genet. 2012 May 4;90(5):907-14. doi: 10.1016/j.ajhg.2012.04.002. PMID:22560091 doi:10.1016/j.ajhg.2012.04.002
- ↑ Cho H, Kehrl JH. Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division. J Cell Biol. 2007 Jul 16;178(2):245-55. PMID:17635935 doi:10.1083/jcb.200604114
- ↑ Jia M, Li J, Zhu J, Wen W, Zhang M, Wang W. Crystal structures of the scaffolding protein LGN reveal the general mechanism by which GoLoco binding motifs inhibit the release of GDP from Gαi. J Biol Chem. 2012 Oct 26;287(44):36766-76. PMID:22952234 doi:10.1074/jbc.M112.391607
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