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Structure paper

TitleStructure of the active form of human origin recognition complex and its ATPase motor module.
Journal, issue, pagesElife, Vol. 6, Year 2017
Publish dateJan 23, 2017
AuthorsAnte Tocilj / Kin Fan On / Zuanning Yuan / Jingchuan Sun / Elad Elkayam / Huilin Li / Bruce Stillman / Leemor Joshua-Tor /
PubMed AbstractBinding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of ...Binding of the Origin Recognition Complex (ORC) to origins of replication marks the first step in the initiation of replication of the genome in all eukaryotic cells. Here, we report the structure of the active form of human ORC determined by X-ray crystallography and cryo-electron microscopy. The complex is composed of an ORC1/4/5 motor module lobe in an organization reminiscent of the DNA polymerase clamp loader complexes. A second lobe contains the ORC2/3 subunits. The complex is organized as a double-layered shallow corkscrew, with the AAA+ and AAA+-like domains forming one layer, and the winged-helix domains (WHDs) forming a top layer. CDC6 fits easily between ORC1 and ORC2, completing the ring and the DNA-binding channel, forming an additional ATP hydrolysis site. Analysis of the ATPase activity of the complex provides a basis for understanding ORC activity as well as molecular defects observed in Meier-Gorlin Syndrome mutations.
External linksElife / PubMed:28112645 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.394 - 18.0 Å
Structure data

EMDB-8523:
Structure of the active form of human Origin Recognition Complex and its ATPase motor module
Method: EM (single particle) / Resolution: 16.9 Å

EMDB-8541, PDB-5ujm:
Structure of the active form of human Origin Recognition Complex and its ATPase motor module
Method: EM (single particle) / Resolution: 18.0 Å

PDB-5uj7:
Structure of the active form of human Origin Recognition Complex ATPase motor module, complex subunitS 1, 4, 5
Method: X-RAY DIFFRACTION / Resolution: 3.394 Å

PDB-5uj8:
Human Origin Recognition Complex subunits 2 and 3
Method: X-RAY DIFFRACTION / Resolution: 6 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-K:
Unknown entry

Source
  • homo sapiens (human)
KeywordsDNA BINDING PROTEIN / Replication / DNA-binding / AAA+ ATPase / HYDROLASE / ORC / ATPase

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