WD 40 domain of RqkA regulates its kinase activity and role in extraordinary radioresistance inDeinococcus radiodurans

Abstract

35RqkA, a DNA damage responsive Serine / Threonine kinase is characterized for its role in 36 DNA repair and cell division in D. radiodurans. It has a unique combination of a kinase 37 domain at N-terminus and a WD40 type domain at C-terminus joined through a linker. WD40 38 domain is comprised of eight β propeller repeats held together via "tryptophan-docking 39 motifs" and forming a typical 'velcro' closure structure. RqkA mutants lacking the WD40 40 region (hereafter referred to as WD mutant) could not complement RqkA loss in γ radiation 41 resistance in D. radiodurans and lacked γ radiation mediated activation of kinase activity in 42 vivo. WD mutants failed to phosphorylate its cognate substrate (e.g. DrRecA) in surrogate E. 43 coli cells. Further, unlike wild type enzyme, the kinase activity of its WD40 mutants was not 44 stimulated by Pyrroloquinoline quinine (PQQ) indicating the role of the WD motifs in PQQ 45 interaction and stimulation of its kinase activity. Together, results highlighted the importance 46 of the WD40 domain in the regulation of RqkA kinase signaling functions in vivo and thus 47