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Distinct Z-DNA binding mode of a PKR-like protein kinase containing a Z-DNA binding domain (PKZ).


ABSTRACT: Double-stranded ribonucleic acid-activated protein kinase (PKR) downregulates translation as a defense mechanism against viral infection. In fish species, PKZ, a PKR-like protein kinase containing left-handed deoxyribonucleic acid (Z-DNA) binding domains, performs a similar role in the antiviral response. To understand the role of PKZ in Z-DNA recognition and innate immune response, we performed structural and functional studies of the Z-DNA binding domain (Z?) of PKZ from Carassius auratus (caZ?PKZ). The 1.7-Å resolution crystal structure of caZ?PKZ:Z-DNA revealed that caZ?PKZ shares the overall fold with other Z?, but has discrete structural features that differentiate its DNA binding mode from others. Functional analyses of caZ?PKZ and its mutants revealed that caZ?PKZ mediates the fastest B-to-Z transition of DNA among Z?, and the minimal interaction for Z-DNA recognition is mediated by three backbone phosphates and six residues of caZ?PKZ. Structure-based mutagenesis and B-to-Z transition assays confirmed that Lys56 located in the ?-wing contributes to its fast B-to-Z transition kinetics. Investigation of the DNA binding kinetics of caZ?PKZ further revealed that the B-to-Z transition rate is positively correlated with the association rate constant. Taking these results together, we conclude that the positive charge in the ?-wing largely affects fast B-to-Z transition activity by enhancing the DNA binding rate.

SUBMITTER: Kim D 

PROVIDER: S-EPMC4027156 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Distinct Z-DNA binding mode of a PKR-like protein kinase containing a Z-DNA binding domain (PKZ).

Kim Doyoun D   Hur Jeonghwan J   Park Kwangsoo K   Bae Sangsu S   Shin Donghyuk D   Ha Sung Chul SC   Hwang Hye-Yeon HY   Hohng Sungchul S   Lee Joon-Hwa JH   Lee Sangho S   Kim Yang-Gyun YG   Kim Kyeong Kyu KK  

Nucleic acids research 20140320 9


Double-stranded ribonucleic acid-activated protein kinase (PKR) downregulates translation as a defense mechanism against viral infection. In fish species, PKZ, a PKR-like protein kinase containing left-handed deoxyribonucleic acid (Z-DNA) binding domains, performs a similar role in the antiviral response. To understand the role of PKZ in Z-DNA recognition and innate immune response, we performed structural and functional studies of the Z-DNA binding domain (Zα) of PKZ from Carassius auratus (caZ  ...[more]

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