PDBsum entry 4xgc

DNA binding protein

PDB id: 4xgc

Contents

Protein chains

281 a.a.

567 a.a.

402 a.a.

310 a.a.

37 a.a.

19 a.a.

440 a.a.

Metals

__K

_CL

PDB id:

4xgc

Name:

DNA binding protein

Title:

Crystal structure of the eukaryotic origin recognition complex

Structure:

Origin recognition complex subunit 2. Chain: b. Fragment: residues 266-618. Synonym: dmorc2. Engineered: yes. Origin recognition complex subunit 3. Chain: c. Fragment: residues 47-721. Synonym: fi24229p1,gh28787p,lp02234p1,latheo.

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: orc2, cg3041. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Gene: lat, cg34315-rb, lat-ra, cg4088, dmel_cg4088. Gene: orc5, cg7833. Gene: orc1, cg10667.

Resolution:

3.50Å R-factor: 0.225 R-free: 0.258

Authors:

F.Bleichert,M.R.Botchan,J.M.Berger

Key ref:

F.Bleichert et al. (2015). Crystal structure of the eukaryotic origin recognition complex. Nature, 519, 321-326. PubMed id: 25762138 DOI: 10.1038/nature14239

Date:

30-Dec-14 Release date: 01-Apr-15

Protein chain

Q24168  (ORC2_DROME) -  Origin recognition complex subunit 2 from Drosophila melanogaster

Seq: 618 a.a.

Struc: 281 a.a.

Protein chain

Q7K2L1  (Q7K2L1_DROME) -  Origin recognition complex subunit 3 from Drosophila melanogaster

Seq: 721 a.a.

Struc: 567 a.a.*

Protein chain

Q24169  (ORC5_DROME) -  Origin recognition complex subunit 5 from Drosophila melanogaster

Seq: 460 a.a.

Struc: 402 a.a.

Protein chain

O16810  (ORC1_DROME) -  Origin recognition complex subunit 1 from Drosophila melanogaster

Seq: 924 a.a.

Struc: 310 a.a.

Protein chain

No UniProt id for this chain

Struc: 37 a.a.

Protein chain

Q9Y1B2  (ORC6_DROME) -  Origin recognition complex subunit 6 from Drosophila melanogaster

Seq: 257 a.a.

Struc: 19 a.a.

Protein chain

Q9W102  (Q9W102_DROME) -  Origin recognition complex subunit 4 from Drosophila melanogaster

Seq: 459 a.a.

Struc: 440 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chain D: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.
• Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1038/nature14239

Nature 519:321-326 (2015)

PubMed id: 25762138

Crystal structure of the eukaryotic origin recognition complex.

F.Bleichert, M.R.Botchan, J.M.Berger.

ABSTRACT

Initiation of cellular DNA replication is tightly controlled to sustain genomic integrity. In eukaryotes, the heterohexameric origin recognition complex (ORC) is essential for coordinating replication onset. Here we describe the crystal structure of Drosophila ORC at 3.5 Å resolution, showing that the 270 kilodalton initiator core complex comprises a two-layered notched ring in which a collar of winged-helix domains from the Orc1-5 subunits sits atop a layer of AAA+ (ATPases associated with a variety of cellular activities) folds. Although canonical inter-AAA+ domain interactions exist between four of the six ORC subunits, unanticipated features are also evident. These include highly interdigitated domain-swapping interactions between the winged-helix folds and AAA+ modules of neighbouring protomers, and a quasi-spiral arrangement of DNA binding elements that circumnavigate an approximately 20 Å wide channel in the centre of the complex. Comparative analyses indicate that ORC encircles DNA, using its winged-helix domain face to engage the mini-chromosome maintenance 2-7 (MCM2-7) complex during replicative helicase loading; however, an observed out-of-plane rotation of more than 90° for the Orc1 AAA+ domain disrupts interactions with catalytic amino acids in Orc4, narrowing and sealing off entry into the central channel. Prima facie, our data indicate that Drosophila ORC can switch between active and autoinhibited conformations, suggesting a novel means for cell cycle and/or developmental control of ORC functions.