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Crystal structure of PprA W183R mutant form 2Crystal structure of PprA W183R mutant form 2
Structural highlights
FunctionPPRA_DEIRA dsDNA-binding protein that contributes to the ionizing radiation resistance of D.radiodurans. Plays a role in DNA repair and genome reconstitution, and is necessary for recovery from severe genomic fragmentation as a result of exposure to severe levels of ionizing radiation. In vitro, binds to double-stranded DNA carrying strand breaks and stimulates the DNA end-joining reaction catalyzed by DNA ligases. Thus, PprA plays a critical role in a non-homologous end-joining (NHEJ) pathway for the repair of radiation-induced DNA double-strands breaks. Cannot bind to dsDNA without strand breaks or single-stranded DNA.[1] [2] Publication Abstract from PubMedPleiotropic protein promoting DNA repair A (PprA) is a key protein facilitating the extreme radiation resistance of Deinococcus radiodurans. PprA is a unique protein to the genus Deinococcus and exists as an oligomer ranging from a tetramer to an approximately 100-mer depending on protein concentrations. Here, the X-ray crystal structure of PprA was determined to clarify how PprA confers radiation resistance. The tertiary structure of dimeric PprA was elucidated by using mutants obtained with random and site-directed mutagenesis methods (W183R and A139R); these mutants have disabled DNA binding and polymerization functions. Because the mutant A139R and W183R proteins have dimeric assemblies with 2 different interfaces (Interfaces 1 and 2), the linear and oligomerized PprA model was constructed as a left-handed face-to-face periodic screw structure. In addition, the linear structure in solution was confirmed by small-angle scattering experiments. The site-directed mutational analysis identified essential basic amino acids for DNA binding. These analytical data support the hypothesis that a complex assembly of PprA molecules, which are extended and have a screw structure, surrounds and stretches the DNA strand, acting as a novel guide to colocalize the DNA strands for efficient DNA repairs.-Adachi, M., Shimizu, R., Shibazaki, C., Satoh, K., Fujiwara, S., Arai, S., Narumi, I., Kuroki, R. Extended structure of pleiotropic DNA repair-promoting protein PprA from Deinococcus radiodurans. Extended structure of pleiotropic DNA repair-promoting protein PprA from Deinococcus radiodurans.,Adachi M, Shimizu R, Shibazaki C, Satoh K, Fujiwara S, Arai S, Narumi I, Kuroki R FASEB J. 2018 Nov 27:fj201801506R. doi: 10.1096/fj.201801506R. PMID:30481062[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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