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| | ==Crystal structure of SeqA bound to DNA== | | ==Crystal structure of SeqA bound to DNA== |
| - | <StructureSection load='3fmt' size='340' side='right' caption='[[3fmt]], [[Resolution|resolution]] 2.98Å' scene=''> | + | <StructureSection load='3fmt' size='340' side='right'caption='[[3fmt]], [[Resolution|resolution]] 2.98Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3fmt]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FMT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3FMT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3fmt]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3FMT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3FMT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr> |
| | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=6MA:N6-METHYL-DEOXY-ADENOSINE-5-MONOPHOSPHATE'>6MA</scene></td></tr> | | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=6MA:N6-METHYL-DEOXY-ADENOSINE-5-MONOPHOSPHATE'>6MA</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lrr|1lrr]], [[1xrx|1xrx]], [[1j3e|1j3e]], [[1iu3|1iu3]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1lrr|1lrr]], [[1xrx|1xrx]], [[1j3e|1j3e]], [[1iu3|1iu3]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b0687, JW0674, seqA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b0687, JW0674, seqA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=3fmt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fmt OCA], [http://pdbe.org/3fmt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fmt RCSB], [http://www.ebi.ac.uk/pdbsum/3fmt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fmt ProSAT]</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=3fmt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fmt OCA], [https://pdbe.org/3fmt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3fmt RCSB], [https://www.ebi.ac.uk/pdbsum/3fmt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3fmt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SEQA_ECOLI SEQA_ECOLI]] Negative regulator of replication initiation, which contributes to regulation of DNA replication and ensures that replication initiation occurs exactly once per chromosome per cell cycle. Binds to pairs of hemimethylated GATC sequences in the oriC region, thus preventing assembly of replication proteins and re-initiation at newly replicated origins. Repression is relieved when the region becomes fully methylated. Can also bind to hemimethylated GATC sequences outside of oriC region. Binds, with less affinity, to fully methylated GATC sites and affects timing of replication. May play a role in chromosome organization and gene regulation.<ref>PMID:8011018</ref> <ref>PMID:7891562</ref> <ref>PMID:7553853</ref> <ref>PMID:11080170</ref> <ref>PMID:10931282</ref> <ref>PMID:20689753</ref> | + | [[https://www.uniprot.org/uniprot/SEQA_ECOLI SEQA_ECOLI]] Negative regulator of replication initiation, which contributes to regulation of DNA replication and ensures that replication initiation occurs exactly once per chromosome per cell cycle. Binds to pairs of hemimethylated GATC sequences in the oriC region, thus preventing assembly of replication proteins and re-initiation at newly replicated origins. Repression is relieved when the region becomes fully methylated. Can also bind to hemimethylated GATC sequences outside of oriC region. Binds, with less affinity, to fully methylated GATC sites and affects timing of replication. May play a role in chromosome organization and gene regulation.<ref>PMID:8011018</ref> <ref>PMID:7891562</ref> <ref>PMID:7553853</ref> <ref>PMID:11080170</ref> <ref>PMID:10931282</ref> <ref>PMID:20689753</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/fm/3fmt_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fm/3fmt_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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| | </StructureSection> | | </StructureSection> |
| | [[Category: Ecoli]] | | [[Category: Ecoli]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Austin, S]] | | [[Category: Austin, S]] |
| | [[Category: Brendler, T]] | | [[Category: Brendler, T]] |
| Structural highlights
Function
[SEQA_ECOLI] Negative regulator of replication initiation, which contributes to regulation of DNA replication and ensures that replication initiation occurs exactly once per chromosome per cell cycle. Binds to pairs of hemimethylated GATC sequences in the oriC region, thus preventing assembly of replication proteins and re-initiation at newly replicated origins. Repression is relieved when the region becomes fully methylated. Can also bind to hemimethylated GATC sequences outside of oriC region. Binds, with less affinity, to fully methylated GATC sites and affects timing of replication. May play a role in chromosome organization and gene regulation.[1] [2] [3] [4] [5] [6]
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
SeqA is a negative regulator of DNA replication in Escherichia coli and related bacteria that functions by sequestering the origin of replication and facilitating its resetting after every initiation event. Inactivation of the seqA gene leads to unsynchronized rounds of replication, abnormal localization of nucleoids and increased negative superhelicity. Excess SeqA also disrupts replication synchrony and affects cell division. SeqA exerts its functions by binding clusters of transiently hemimethylated GATC sequences generated during replication. However, the molecular mechanisms that trigger formation and disassembly of such complex are unclear. We present here the crystal structure of a dimeric mutant of SeqA [SeqADelta(41-59)-A25R] bound to tandem hemimethylated GATC sites. The structure delineates how SeqA forms a high-affinity complex with DNA and it suggests why SeqA only recognizes GATC sites at certain spacings. The SeqA-DNA complex also unveils additional protein-protein interaction surfaces that mediate the formation of higher ordered complexes upon binding to newly replicated DNA. Based on this data, we propose a model describing how SeqA interacts with newly replicated DNA within the origin of replication and at the replication forks.
Structural insights into the cooperative binding of SeqA to a tandem GATC repeat.,Chung YS, Brendler T, Austin S, Guarne A Nucleic Acids Res. 2009 Jun;37(10):3143-52. Epub 2009 Mar 20. PMID:19304745[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lu M, Campbell JL, Boye E, Kleckner N. SeqA: a negative modulator of replication initiation in E. coli. Cell. 1994 May 6;77(3):413-26. PMID:8011018
- ↑ von Freiesleben U, Rasmussen KV, Schaechter M. SeqA limits DnaA activity in replication from oriC in Escherichia coli. Mol Microbiol. 1994 Nov;14(4):763-72. PMID:7891562
- ↑ Slater S, Wold S, Lu M, Boye E, Skarstad K, Kleckner N. E. coli SeqA protein binds oriC in two different methyl-modulated reactions appropriate to its roles in DNA replication initiation and origin sequestration. Cell. 1995 Sep 22;82(6):927-36. PMID:7553853
- ↑ Brendler T, Sawitzke J, Sergueev K, Austin S. A case for sliding SeqA tracts at anchored replication forks during Escherichia coli chromosome replication and segregation. EMBO J. 2000 Nov 15;19(22):6249-58. PMID:11080170 doi:10.1093/emboj/19.22.6249
- ↑ Skarstad K, Lueder G, Lurz R, Speck C, Messer W. The Escherichia coli SeqA protein binds specifically and co-operatively to two sites in hemimethylated and fully methylated oriC. Mol Microbiol. 2000 Jun;36(6):1319-26. PMID:10931282
- ↑ Sanchez-Romero MA, Busby SJ, Dyer NP, Ott S, Millard AD, Grainger DC. Dynamic distribution of seqa protein across the chromosome of escherichia coli K-12. MBio. 2010 May 18;1(1). pii: e00012-10. doi: 10.1128/mBio.00012-10. PMID:20689753 doi:10.1128/mBio.00012-10
- ↑ Chung YS, Brendler T, Austin S, Guarne A. Structural insights into the cooperative binding of SeqA to a tandem GATC repeat. Nucleic Acids Res. 2009 Jun;37(10):3143-52. Epub 2009 Mar 20. PMID:19304745 doi:10.1093/nar/gkp151
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