6kvg

From Proteopedia

(Difference between revisions)

Current revision

The solution structure of human Orc6

Structural highlights

6kvg is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

ORC6_HUMAN Ear-patella-short stature syndrome. Defects in ORC6 are the cause of Meier-Gorlin syndrome type 3 (MGORS3) [MIM:613803. MGORS3 is a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.^[1]

Function

ORC6_HUMAN Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.

Publication Abstract from PubMed

The six-subunit origin recognition complex (ORC), a DNA replication initiator, defines the localization of the origins of replication in eukaryotes. The Orc6 subunit is the smallest and the least conserved among ORC subunits. It is required for DNA replication and essential for viability in all species. Orc6 in metazoans carries a structural homology with transcription factor TFIIB and can bind DNA on its own. Here, we report a solution structure of the full-length human Orc6 (HsOrc6) alone and in a complex with DNA. We further showed that human Orc6 is composed of three independent domains: N-terminal, middle and C-terminal (HsOrc6-N, HsOrc6-M and HsOrc6-C). We also identified a distinct DNA-binding domain of human Orc6, named as HsOrc6-DBD. The detailed analysis of the structure revealed novel amino acid clusters important for the interaction with DNA. Alterations of these amino acids abolish DNA-binding ability of Orc6 and result in reduced levels of DNA replication. We propose that Orc6 is a DNA-binding subunit of human/metazoan ORC and may play roles in targeting, positioning and assembling the functional ORC at the origins.

Structural basis of DNA replication origin recognition by human Orc6 protein binding with DNA.,Xu N, You Y, Liu C, Balasov M, Lun LT, Geng Y, Fung CP, Miao H, Tian H, Choy TT, Shi X, Fan Z, Zhou B, Akhmetova K, Din RU, Yang H, Hao Q, Qian P, Chesnokov I, Zhu G Nucleic Acids Res. 2020 Sep 28. pii: 5912572. doi: 10.1093/nar/gkaa751. PMID:32986843^[2]

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

References

↑ Bicknell LS, Bongers EM, Leitch A, Brown S, Schoots J, Harley ME, Aftimos S, Al-Aama JY, Bober M, Brown PA, van Bokhoven H, Dean J, Edrees AY, Feingold M, Fryer A, Hoefsloot LH, Kau N, Knoers NV, Mackenzie J, Opitz JM, Sarda P, Ross A, Temple IK, Toutain A, Wise CA, Wright M, Jackson AP. Mutations in the pre-replication complex cause Meier-Gorlin syndrome. Nat Genet. 2011 Feb 27;43(4):356-9. doi: 10.1038/ng.775. PMID:21358632 doi:10.1038/ng.775
↑ Xu N, You Y, Liu C, Balasov M, Lun LT, Geng Y, Fung CP, Miao H, Tian H, Choy TT, Shi X, Fan Z, Zhou B, Akhmetova K, Din RU, Yang H, Hao Q, Qian P, Chesnokov I, Zhu G. Structural basis of DNA replication origin recognition by human Orc6 protein binding with DNA. Nucleic Acids Res. 2020 Sep 28. pii: 5912572. doi: 10.1093/nar/gkaa751. PMID:32986843 doi:http://dx.doi.org/10.1093/nar/gkaa751

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/6kvg"

@@ Line 3: / Line 3: @@
 <StructureSection load='6kvg' size='340' side='right'caption='[[6kvg]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KVG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KVG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6kvg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KVG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KVG FirstGlance]. <br>
-</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=6kvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kvg OCA], [http://pdbe.org/6kvg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kvg RCSB], [http://www.ebi.ac.uk/pdbsum/6kvg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kvg ProSAT]</span></td></tr>
+</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=6kvg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kvg OCA], [https://pdbe.org/6kvg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kvg RCSB], [https://www.ebi.ac.uk/pdbsum/6kvg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kvg ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/ORC6_HUMAN ORC6_HUMAN] Ear-patella-short stature syndrome. Defects in ORC6 are the cause of Meier-Gorlin syndrome type 3 (MGORS3) [MIM:[https://omim.org/entry/613803 613803]. MGORS3 is a syndrome characterized by bilateral microtia, aplasia/hypoplasia of the patellae, and severe intrauterine and postnatal growth retardation with short stature and poor weight gain. Additional clinical findings include anomalies of cranial sutures, microcephaly, apparently low-set and simple ears, microstomia, full lips, highly arched or cleft palate, micrognathia, genitourinary tract anomalies, and various skeletal anomalies. While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal.<ref>PMID:21358632</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/ORC6_HUMAN ORC6_HUMAN] Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The six-subunit origin recognition complex (ORC), a DNA replication initiator, defines the localization of the origins of replication in eukaryotes. The Orc6 subunit is the smallest and the least conserved among ORC subunits. It is required for DNA replication and essential for viability in all species. Orc6 in metazoans carries a structural homology with transcription factor TFIIB and can bind DNA on its own. Here, we report a solution structure of the full-length human Orc6 (HsOrc6) alone and in a complex with DNA. We further showed that human Orc6 is composed of three independent domains: N-terminal, middle and C-terminal (HsOrc6-N, HsOrc6-M and HsOrc6-C). We also identified a distinct DNA-binding domain of human Orc6, named as HsOrc6-DBD. The detailed analysis of the structure revealed novel amino acid clusters important for the interaction with DNA. Alterations of these amino acids abolish DNA-binding ability of Orc6 and result in reduced levels of DNA replication. We propose that Orc6 is a DNA-binding subunit of human/metazoan ORC and may play roles in targeting, positioning and assembling the functional ORC at the origins.
+Structural basis of DNA replication origin recognition by human Orc6 protein binding with DNA.,Xu N, You Y, Liu C, Balasov M, Lun LT, Geng Y, Fung CP, Miao H, Tian H, Choy TT, Shi X, Fan Z, Zhou B, Akhmetova K, Din RU, Yang H, Hao Q, Qian P, Chesnokov I, Zhu G Nucleic Acids Res. 2020 Sep 28. pii: 5912572. doi: 10.1093/nar/gkaa751. PMID:32986843<ref>PMID:32986843</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 6kvg" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
 [[Category: Liu C]]

6kvg

From Proteopedia

Current revision

The solution structure of human Orc6

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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