Structural dynamics and determinants of 2-aminoadenine specificity in DNA polymerase DpoZ of vibriophage ϕVC8.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
18 11 2021
18 11 2021
Historique:
accepted:
04
10
2021
revised:
29
09
2021
received:
04
08
2021
pubmed:
10
11
2021
medline:
28
12
2021
entrez:
9
11
2021
Statut:
ppublish
Résumé
All genetic information in cellular life is stored in DNA copolymers composed of four basic building blocks (ATGC-DNA). In contrast, a group of bacteriophages belonging to families Siphoviridae and Podoviridae has abandoned the usage of one of them, adenine (A), replacing it with 2-aminoadenine (Z). The resulting ZTGC-DNA is more stable than its ATGC-DNA counterpart, owing to the additional hydrogen bond present in the 2-aminoadenine:thymine (Z:T) base pair, while the additional amino group also confers resistance to the host endonucleases. Recently, two classes of replicative proteins found in ZTGC-DNA-containing phages were characterized and one of them, DpoZ from DNA polymerase A (PolA) family, was shown to possess significant Z-vs-A specificity. Here, we present the crystallographic structure of the apo form of DpoZ of vibriophage ϕVC8, composed of the 3'-5' exonuclease and polymerase domains. We captured the enzyme in two conformations that involve the tip of the thumb subdomain and the exonuclease domain. We highlight insertions and mutations characteristic of ϕVC8 DpoZ and its close homologues. Through mutagenesis and functional assays we suggest that the preference of ϕVC8 DpoZ towards Z relies on a polymerase backtracking process, more efficient when the nascent base pair is A:T than when it is Z:T.
Identifiants
pubmed: 34751404
pii: 6423936
doi: 10.1093/nar/gkab955
pmc: PMC8599892
doi:
Substances chimiques
DNA, Viral
0
Viral Proteins
0
2-Aminopurine
452-06-2
2,6-diaminopurine
49P95BAU4Z
DNA-Directed DNA Polymerase
EC 2.7.7.7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
11974-11985Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
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