6KVG

The solution structure of human Orc6

Summary for 6KVG

• Entry DOI: 10.2210/pdb6kvg/pdb
• Descriptor: Origin recognition complex subunit 6 (1 entity in total)
• Functional Keywords: orc6, dna, dna binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 28447.19

Authors

Liu, C.,Xu, N.,You, Y.,Zhu, G. (deposition date: 2019-09-04, release date: 2020-09-09, Last modification date: 2024-05-15)

Primary citation

Xu, N.,You, Y.,Liu, C.,Balasov, M.,Lun, L.T.,Geng, Y.,Fung, C.P.,Miao, H.,Tian, H.,Choy, T.T.,Shi, X.,Fan, Z.,Zhou, B.,Akhmetova, K.,Din, R.U.,Yang, H.,Hao, Q.,Qian, P.,Chesnokov, I.,Zhu, G.
Structural basis of DNA replication origin recognition by human Orc6 protein binding with DNA.
Nucleic Acids Res., 48:11146-11161, 2020

PubMed Abstract: The six-subunit origin recognition complex (ORC), a DNA replication initiator, defines the localization of the origins of replication in eukaryotes. The Orc6 subunit is the smallest and the least conserved among ORC subunits. It is required for DNA replication and essential for viability in all species. Orc6 in metazoans carries a structural homology with transcription factor TFIIB and can bind DNA on its own. Here, we report a solution structure of the full-length human Orc6 (HsOrc6) alone and in a complex with DNA. We further showed that human Orc6 is composed of three independent domains: N-terminal, middle and C-terminal (HsOrc6-N, HsOrc6-M and HsOrc6-C). We also identified a distinct DNA-binding domain of human Orc6, named as HsOrc6-DBD. The detailed analysis of the structure revealed novel amino acid clusters important for the interaction with DNA. Alterations of these amino acids abolish DNA-binding ability of Orc6 and result in reduced levels of DNA replication. We propose that Orc6 is a DNA-binding subunit of human/metazoan ORC and may play roles in targeting, positioning and assembling the functional ORC at the origins.

PubMed: 32986843
DOI: 10.1093/nar/gkaa751

Experimental method

SOLUTION NMR