PDBsum entry 7ctf

Replication

PDB id: 7ctf

Contents

Protein chains

102 a.a.

302 a.a.

592 a.a.

406 a.a.

373 a.a.

Ligands

ATP ×2

PDB id:

7ctf

Name:

Replication

Title:

Human origin recognition complex 1-5 state ii

Structure:

Origin recognition complex subunit 1. Chain: a. Synonym: replication control protein 1. Engineered: yes. Origin recognition complex subunit 2. Chain: b. Engineered: yes. Origin recognition complex subunit 3. Chain: c.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: orc1, orc1l, parc1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: orc2, orc2l. Gene: orc3, latheo, orc3l. Gene: orc4, orc4l.

Authors:

J.Cheng,N.Li,X.Wang,J.Hu,Y.Zhai,N.Gao

Key ref:

J.Cheng et al. (2020). Structural insight into the assembly and conformational activation of human origin recognition complex. Cell Discov, 6, 88. PubMed id: 33298899 DOI: 10.1038/s41421-020-00232-3

Date:

18-Aug-20 Release date: 06-Jan-21

Protein chain

Q13415  (ORC1_HUMAN) -  Origin recognition complex subunit 1 from Homo sapiens

Seq: 861 a.a.

Struc: 102 a.a.

Protein chain

Q13416  (ORC2_HUMAN) -  Origin recognition complex subunit 2 from Homo sapiens

Seq: 577 a.a.

Struc: 302 a.a.

Protein chain

Q9UBD5  (ORC3_HUMAN) -  Origin recognition complex subunit 3 from Homo sapiens

Seq: 711 a.a.

Struc: 592 a.a.

Protein chain

O43929  (ORC4_HUMAN) -  Origin recognition complex subunit 4 from Homo sapiens

Seq: 436 a.a.

Struc: 406 a.a.

Protein chain

O43913  (ORC5_HUMAN) -  Origin recognition complex subunit 5 from Homo sapiens

Seq: 435 a.a.

Struc: 373 a.a.

DOI no: 10.1038/s41421-020-00232-3

Cell Discov 6:88 (2020)

PubMed id: 33298899

Structural insight into the assembly and conformational activation of human origin recognition complex.

J.Cheng, N.Li, X.Wang, J.Hu, Y.Zhai, N.Gao.

ABSTRACT

The function of the origin recognition complex (ORC) in DNA replication is highly conserved in recognizing and marking the initiation sites. The detailed molecular mechanisms by which human ORC is reconfigured into a state competent for origin association remain largely unknown. Here, we present structural characterizations of human ORC1-5 and ORC2-5 assemblies. ORC2-5 exhibits a tightly autoinhibited conformation with the winged-helix domain of ORC2 completely blocking the central DNA-binding channel. The binding of ORC1 partially relieves the autoinhibitory effect of ORC2-5 through remodeling ORC2-WHD, which makes ORC2-WHD away from the central channel creating a still autoinhibited but more dynamic structure. In particular, the AAA+ domain of ORC1 is highly flexible to sample a variety of conformations from inactive to potentially active states. These results provide insights into the detailed mechanisms regulating the autoinhibition of human ORC and its subsequent activation for DNA binding.