5OGS

Crystal structure of human AND-1 SepB domain

Summary for 5OGS

• Entry DOI: 10.2210/pdb5ogs/pdb
• Descriptor: WD repeat and HMG-box DNA-binding protein 1, MALONATE ION (3 entities in total)
• Functional Keywords: dna replication/adaptor protein/beta propeller domain, replication
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus, nucleoplasm : O75717
• Total number of polymer chains: 1
• Total formula weight: 56334.38

Authors

Pellegrini, L.,Simon, A.C. (deposition date: 2017-07-13, release date: 2017-11-29, Last modification date: 2024-01-17)

Primary citation

Kilkenny, M.L.,Simon, A.C.,Mainwaring, J.,Wirthensohn, D.,Holzer, S.,Pellegrini, L.
The human CTF4-orthologue AND-1 interacts with DNA polymerase alpha /primase via its unique C-terminal HMG box.
Open Biol, 7:-, 2017

PubMed Abstract: A dynamic multi-protein assembly known as the replisome is responsible for DNA synthesis in eukaryotic cells. In yeast, the hub protein Ctf4 bridges DNA helicase and DNA polymerase and recruits factors with roles in metabolic processes coupled to DNA replication. An important question in DNA replication is the extent to which the molecular architecture of the replisome is conserved between yeast and higher eukaryotes. Here, we describe the biochemical basis for the interaction of the human CTF4-orthologue AND-1 with DNA polymerase α (Pol α)/primase, the replicative polymerase that initiates DNA synthesis. AND-1 has maintained the trimeric structure of yeast Ctf4, driven by its conserved SepB domain. However, the primary interaction of AND-1 with Pol α/primase is mediated by its C-terminal HMG box, unique to mammalian AND-1, which binds the B subunit, at the same site targeted by the SV40 T-antigen for viral replication. In addition, we report a novel DNA-binding activity in AND-1, which might promote the correct positioning of Pol α/primase on the lagging-strand template at the replication fork. Our findings provide a biochemical basis for the specific interaction between two critical components of the human replisome, and indicate that important principles of replisome architecture have changed significantly in evolution.

PubMed: 29167311
DOI: 10.1098/rsob.170217

Experimental method

X-RAY DIFFRACTION (2.503 Å)