5gva

WD40 domain of human AND-1

spinqualitylabelsall models 5gva, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5gva is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 5gvb Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [WDHD1_HUMAN] Acts as a replication initiation factor that brings together the MCM2-7 helicase and the DNA polymerase alpha/primase complex in order to initiate DNA replication. Publication Abstract from PubMed DNA replication in eukaryotic cells is performed by a multiprotein complex called the replisome, which consists of helicases, polymerases, and adaptor molecules. Human acidic nucleoplasmic DNA-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 alpha (pol alpha) to the DNA helicase complex (Cdc45-MCM2-7-GINS, 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 alpha. 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 in vitro, 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. The structure and polymerase-recognition mechanism of the crucial adaptor protein AND-1 in the human replisome.,Guan C, Li J, Sun D, Liu Y, Liang H J Biol Chem. 2017 Jun 9;292(23):9627-9636. doi: 10.1074/jbc.M116.758524. Epub, 2017 Apr 5. PMID:28381552 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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