2.0 Å resolution crystal structure of human polκ reveals a new catalytic function of N-clasp in DNA replication
| العنوان: | 2.0 Å resolution crystal structure of human polκ reveals a new catalytic function of N-clasp in DNA replication |
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| المؤلفون: | Vikash Jha, Hong Ling |
| المصدر: | Scientific Reports, Vol 8, Iss 1, Pp 1-9 (2018) Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, DNA Replication, DNA polymerase, lcsh:Medicine, DNA-Directed DNA Polymerase, medicine.disease_cause, Article, 03 medical and health sciences, chemistry.chemical_compound, Catalytic Domain, medicine, Humans, A-DNA, Nucleotide, lcsh:Science, Ternary complex, Polymerase, chemistry.chemical_classification, Mutation, Multidisciplinary, 030102 biochemistry & molecular biology, biology, lcsh:R, DNA replication, DNA, 3. Good health, Cell biology, Molecular Docking Simulation, 030104 developmental biology, chemistry, biology.protein, lcsh:Q |
| الوصف: | Human polymerase kappa (polκ) is a distinct Y-family DNA polymerase with a unique N-terminal N-clasp domain. The N-clasp renders polκ’s high efficiency and accuracy in DNA replication and lesion bypass. How N-clasp empowers polκ in replication remains unclear due to the disordering of N-clasp. Here, we present a 2.0-Å resolution crystal structure of a polκ ternary complex with DNA and an incoming nucleotide. The structure-function study reveals an ordered N-clasp domain that brings conserved and functionally important residues in contact with the replicating basepair in the active site and contributes to the nucleotidyl transfer reaction. Particularly, a fully ordered Lys25 from the N-clasp domain is in H-bonding with the α- and γ-phosphates of the incoming nucleotide. K25A mutation reduces the polymerase activity of polκ significantly. This lysine is structurally analogous to a conserved lysine in the A-family DNA polymerases in the closed form. In contrast, Lys25 in the previous structures of polκ does not have any contacts with the incoming nucleotide, resembling an open form of a DNA polymerase. Based on structural and functional similarity, we propose a local open/closed mechanism for polκ in DNA replication catalysis, which mimics the common mechanism for all DNA polymerases. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| DOI: | 10.1038/s41598-018-33371-5 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2db6f4527bf75a4587f0cb3af44ffc84 http://link.springer.com/article/10.1038/s41598-018-33371-5 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2db6f4527bf75a4587f0cb3af44ffc84 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-018-33371-5 |