5OGS

Crystal structure of human AND-1 SepB domain

5OGS の概要

• エントリーDOI: 10.2210/pdb5ogs/pdb
• 分子名称: WD repeat and HMG-box DNA-binding protein 1, MALONATE ION (3 entities in total)
• 機能のキーワード: dna replication/adaptor protein/beta propeller domain, replication
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus, nucleoplasm : O75717
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 56334.38

構造登録者

Pellegrini, L.,Simon, A.C. (登録日: 2017-07-13, 公開日: 2017-11-29, 最終更新日: 2024-01-17)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.503 Å)