5mk5

From Proteopedia

(Difference between revisions)

Revision as of 07:35, 25 June 2021

Structures of DHBN domain of human BLM helicase

Structural highlights

5mk5 is a 4 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 5m1v. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	BLM, RECQ2, RECQL3 (HUMAN)
Activity:	DNA helicase, with EC number 3.6.4.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[BLM_HUMAN] Bloom syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

[BLM_HUMAN] Participates in DNA replication and repair. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction. Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA. Negatively regulates sister chromatid exchange (SCE).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Helicases play a critical role in processes such as replication or recombination by unwinding double-stranded DNA; mutations of these genes can therefore have devastating biological consequences. In human, mutations in genes of three members of the RecQ family helicases (blm, wrn and recq4) give rise to three strikingly distinctive clinical phenotypes: Bloom syndrome, Werner syndrome and Rothmund-Thomson syndrome, respectively. However, the molecular basis for these varying phenotypic outcomes is unclear, in part because a full mechanistic description of helicase activity is lacking. As the helicase core domains are highly conserved, it has been postulated that functional differences among family members might be explained by significant differences in the N-terminal domains, but these domains are poorly characterized. To help fill this gap, we now describe bioinformatics, biochemical, and structural data for three vertebrate BLM proteins. We pair high resolution crystal structures with SAXS analysis to describe an internal, highly conserved sequence we term the Dimerization Helical Bundle in N-terminal domain (DHBN). We show that, despite the N-terminal domain being loosely structured and potentially lacking a defined three dimensional structure in general, the DHBN exists as a dimeric structure required for higher order oligomer assembly. Interestingly, the unwinding amplitude and rate decrease as BLM is assembled from dimer into hexamer, and also, the stable DHBN dimer can be dissociated upon ATP hydrolysis. Thus, the structural and biochemical characterizations of N-terminal domains will provide new insights into how the N-terminal domain affects the structural and functional organization of the full BLM molecule.

A Helical Bundle in the N-terminal Domain of the BLM Helicase Mediates Dimer and Potentially Hexamer Formation.,Shi J, Chen WF, Zhang B, Fan SH, Ai X, Liu NN, Rety S, Xi XG J Biol Chem. 2017 Feb 22. pii: jbc.M116.761510. doi: 10.1074/jbc.M116.761510. PMID:28228481^[5]

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

References

↑ Karow JK, Chakraverty RK, Hickson ID. The Bloom's syndrome gene product is a 3'-5' DNA helicase. J Biol Chem. 1997 Dec 5;272(49):30611-4. PMID:9388193
↑ Langland G, Elliott J, Li Y, Creaney J, Dixon K, Groden J. The BLM helicase is necessary for normal DNA double-strand break repair. Cancer Res. 2002 May 15;62(10):2766-70. PMID:12019152
↑ Nimonkar AV, Genschel J, Kinoshita E, Polaczek P, Campbell JL, Wyman C, Modrich P, Kowalczykowski SC. BLM-DNA2-RPA-MRN and EXO1-BLM-RPA-MRN constitute two DNA end resection machineries for human DNA break repair. Genes Dev. 2011 Feb 15;25(4):350-62. doi: 10.1101/gad.2003811. PMID:21325134 doi:http://dx.doi.org/10.1101/gad.2003811
↑ Wan L, Han J, Liu T, Dong S, Xie F, Chen H, Huang J. Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair. Proc Natl Acad Sci U S A. 2013 Jun 25;110(26):10646-51. doi:, 10.1073/pnas.1220921110. Epub 2013 Mar 18. PMID:23509288 doi:http://dx.doi.org/10.1073/pnas.1220921110
↑ Shi J, Chen WF, Zhang B, Fan SH, Ai X, Liu NN, Rety S, Xi XG. A Helical Bundle in the N-terminal Domain of the BLM Helicase Mediates Dimer and Potentially Hexamer Formation. J Biol Chem. 2017 Feb 22. pii: jbc.M116.761510. doi: 10.1074/jbc.M116.761510. PMID:28228481 doi:http://dx.doi.org/10.1074/jbc.M116.761510

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5mk5"

@@ Line 3: / Line 3: @@
 <StructureSection load='5mk5' size='340' side='right'caption='[[5mk5]], [[Resolution|resolution]] 2.16&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5mk5]] is a 4 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=5MK5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MK5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5mk5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5m1v 5m1v]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MK5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MK5 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BLM, RECQ2, RECQL3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BLM, RECQ2, RECQL3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/DNA_helicase DNA helicase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.12 3.6.4.12] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mk5 OCA], [http://pdbe.org/5mk5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mk5 RCSB], [http://www.ebi.ac.uk/pdbsum/5mk5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mk5 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=5mk5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mk5 OCA], [https://pdbe.org/5mk5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mk5 RCSB], [https://www.ebi.ac.uk/pdbsum/5mk5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mk5 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/BLM_HUMAN BLM_HUMAN]] Bloom syndrome. The disease is caused by mutations affecting the gene represented in this entry.
+[[https://www.uniprot.org/uniprot/BLM_HUMAN BLM_HUMAN]] Bloom syndrome. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/BLM_HUMAN BLM_HUMAN]] Participates in DNA replication and repair. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction. Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA. Negatively regulates sister chromatid exchange (SCE).<ref>PMID:9388193</ref> <ref>PMID:12019152</ref> <ref>PMID:21325134</ref> <ref>PMID:23509288</ref>
+[[https://www.uniprot.org/uniprot/BLM_HUMAN BLM_HUMAN]] Participates in DNA replication and repair. Exhibits a magnesium-dependent ATP-dependent DNA-helicase activity that unwinds single- and double-stranded DNA in a 3'-5' direction. Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA. Negatively regulates sister chromatid exchange (SCE).<ref>PMID:9388193</ref> <ref>PMID:12019152</ref> <ref>PMID:21325134</ref> <ref>PMID:23509288</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

5mk5

From Proteopedia

Revision as of 07:35, 25 June 2021

Structures of DHBN domain of human BLM helicase

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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