5GVB

SepB domain of human AND-1

Summary for 5GVB

• Entry DOI: 10.2210/pdb5gvb/pdb
• Related: 5GVA
• Descriptor: WD repeat and HMG-box DNA-binding protein 1 (2 entities in total)
• Functional Keywords: sepb, wd40, replication, peptide binding protein
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus, nucleoplasm : O75717
• Total number of polymer chains: 1
• Total formula weight: 50514.88

Authors

Guan, C.C.,Li, J. (deposition date: 2016-09-05, release date: 2017-04-19, Last modification date: 2024-11-13)

Primary citation

Guan, C.,Li, J.,Sun, D.,Liu, Y.,Liang, H.
The structure and polymerase-recognition mechanism of the crucial adaptor protein AND-1 in the human replisome.
J. Biol. Chem., 292:9627-9636, 2017

PubMed Abstract: DNA replication in eukaryotic cells is performed by a multiprotein complex called the replisome, which consists of helicases, polymerases, and adaptor molecules. Human cidic ucleoplasmic NA-binding protein 1 (AND-1), also known as WD repeat and high mobility group (HMG)-box DNA-binding protein 1 (WDHD1), is an adaptor molecule crucial for DNA replication. Although structural information for the AND-1 yeast ortholog is available, the mechanistic details for how human AND-1 protein anchors the lagging-strand DNA polymerase α (pol α) to the DNA helicase complex (dc45-CM2-7-INS, CMG) await elucidation. Here, we report the structures of the N-terminal WD40 and SepB domains of human AND-1, as well as a biochemical analysis of the C-terminal HMG domain. We show that AND-1 exists as a homotrimer mediated by the SepB domain. Mutant study results suggested that a positively charged groove within the SepB domain provides binding sites for pol α. Different from its ortholog protein in budding yeast, human AND-1 is recruited to the CMG complex, mediated by unknown participants other than Go Ichi Ni San. In addition, we show that AND-1 binds to DNA , using its C-terminal HMG domain. In conclusion, our findings provide important insights into the mechanistic details of human AND-1 function, advancing our understanding of replisome formation during eukaryotic replication.

PubMed: 28381552
DOI: 10.1074/jbc.M116.758524

Experimental method

X-RAY DIFFRACTION (2.75 Å)