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4bry

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Revision as of 13:02, 13 March 2019

The Idas:Geminin heterodimeric parallel coiled-coil

Structural highlights

4bry is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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] [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.

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"

@@ 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>
@@ Line 23: / Line 23: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Caillat, C]]
 [[Category: Perrakis, A]]
 [[Category: Cell cycle]]
 [[Category: Dna replication licensing]]

4bry

From Proteopedia

Revision as of 13:02, 13 March 2019

The Idas:Geminin heterodimeric parallel coiled-coil

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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