4bry

From Proteopedia

(Difference between revisions)

Current revision

The Idas:Geminin heterodimeric parallel coiled-coil

Structural highlights

4bry is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.89Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GEMI_HUMAN Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC). It is degraded during the mitotic phase of the cell cycle. Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle.^[1] ^[2] ^[3] Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control.^[4] ^[5] ^[6]

Publication Abstract from PubMed

Geminin is an important regulator of proliferation and differentiation in metazoans, which predominantly inhibits the DNA replication licensing factor Cdt1, preventing genome over-replication. We show that Geminin preferentially forms stable coiled-coil heterodimers with its homologue, Idas. In contrast to Idas:Geminin heterodimers, Idas homodimers are thermodynamically unstable and are unlikely to exist as a stable macromolecule under physiological conditions. The crystal structure of the homology regions of Idas in complex with Geminin showed a tight head-to-head heterodimeric coiled-coil. This Idas:Geminin heterodimer binds Cdt1 less strongly than Geminin:Geminin, still with high affinity (~30nM), but with notably different thermodynamic properties. Consistently, in Xenopus egg extracts, Idas:Geminin is less active in licensing inhibition compared to a Geminin:Geminin homodimer. In human cultured cells, ectopic expression of Idas leads to limited over-replication, which is counteracted by Geminin co-expression. The properties of the Idas:Geminin complex suggest it as the functional form of Idas, and provide a possible mechanism to modulate Geminin activity.

The Geminin and Idas coiled coils preferentially form a heterodimer that inhibits Geminin function in DNA replication licensing.,Caillat C, Pefani ED, Gillespie PJ, Taraviras S, Blow JJ, Lygerou Z, Perrakis A J Biol Chem. 2013 Oct 2. PMID:24064211^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ McGarry TJ, Kirschner MW. Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell. 1998 Jun 12;93(6):1043-53. PMID:9635433
↑ Sugimoto N, Tatsumi Y, Tsurumi T, Matsukage A, Kiyono T, Nishitani H, Fujita M. Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. J Biol Chem. 2004 May 7;279(19):19691-7. Epub 2004 Mar 1. PMID:14993212 doi:10.1074/jbc.M313175200
↑ Zhou B, Liu C, Xu Z, Zhu G. Structural basis for homeodomain recognition by the cell-cycle regulator Geminin. Proc Natl Acad Sci U S A. 2012 May 21. PMID:22615398 doi:10.1073/pnas.1200874109
↑ McGarry TJ, Kirschner MW. Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell. 1998 Jun 12;93(6):1043-53. PMID:9635433
↑ Sugimoto N, Tatsumi Y, Tsurumi T, Matsukage A, Kiyono T, Nishitani H, Fujita M. Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. J Biol Chem. 2004 May 7;279(19):19691-7. Epub 2004 Mar 1. PMID:14993212 doi:10.1074/jbc.M313175200
↑ Zhou B, Liu C, Xu Z, Zhu G. Structural basis for homeodomain recognition by the cell-cycle regulator Geminin. Proc Natl Acad Sci U S A. 2012 May 21. PMID:22615398 doi:10.1073/pnas.1200874109
↑ Caillat C, Pefani ED, Gillespie PJ, Taraviras S, Blow JJ, Lygerou Z, Perrakis A. The Geminin and Idas coiled coils preferentially form a heterodimer that inhibits Geminin function in DNA replication licensing. J Biol Chem. 2013 Oct 2. PMID:24064211 doi:http://dx.doi.org/10.1074/jbc.M113.491928

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4bry"

Categories: Homo sapiens | Large Structures | Caillat C | Perrakis A

@@ Line 1: / Line 1: @@
 ==The Idas:Geminin heterodimeric parallel coiled-coil==
-<StructureSection load='4bry' size='340' side='right' caption='[[4bry]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
+<StructureSection load='4bry' size='340' side='right'caption='[[4bry]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4bry]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BRY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BRY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4bry]] 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=4BRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BRY FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.89&#8491;</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=4bry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bry OCA], [http://pdbe.org/4bry PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4bry RCSB], [http://www.ebi.ac.uk/pdbsum/4bry PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4bry ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=4bry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bry OCA], [https://pdbe.org/4bry PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bry RCSB], [https://www.ebi.ac.uk/pdbsum/4bry PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bry ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GEMI_HUMAN GEMI_HUMAN]] Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC). It is degraded during the mitotic phase of the cell cycle. Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle.<ref>PMID:9635433</ref> <ref>PMID:14993212</ref> <ref>PMID:22615398</ref>   Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control.<ref>PMID:9635433</ref> <ref>PMID:14993212</ref> <ref>PMID:22615398</ref>  [[http://www.uniprot.org/uniprot/MCIN_HUMAN MCIN_HUMAN]] Transcription regulator required for multiciliate cell differentiation. Acts by promoting transcription of genes required for multiciliate cell formation. Probably acts in a multiprotein complex (By similarity). Plays a role in mitotic cell cycle progression by promoting cell cycle exit.
+[https://www.uniprot.org/uniprot/GEMI_HUMAN GEMI_HUMAN] Inhibits DNA replication by preventing the incorporation of MCM complex into pre-replication complex (pre-RC). It is degraded during the mitotic phase of the cell cycle. Its destruction at the metaphase-anaphase transition permits replication in the succeeding cell cycle.<ref>PMID:9635433</ref> <ref>PMID:14993212</ref> <ref>PMID:22615398</ref>   Inhibits the transcriptional activity of a subset of Hox proteins, enrolling them in cell proliferative control.<ref>PMID:9635433</ref> <ref>PMID:14993212</ref> <ref>PMID:22615398</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Caillat, C]]
+[[Category: Large Structures]]
-[[Category: Perrakis, A]]
+[[Category: Caillat C]]
-[[Category: Cell cycle]]
+[[Category: Perrakis A]]
-[[Category: Dna replication licensing]]

4bry

From Proteopedia

Current revision

The Idas:Geminin heterodimeric parallel coiled-coil

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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