Unusual Heme-Binding PAS Domain from YybT Family Proteins

摘要: COG3887 or YybT family proteins are widely distributed among the firmicutes phylum, including such pathogens as Staphylococcus aureus, Streptococcus mutans, and Listeria monocytogenes. contain two N-terminal transmembrane helices three predicted protein domains: a putative Per-ARNT-SIM (PAS) domain, highly degenerate GGDEF DHH/DHHA1 domain (Fig. ​(Fig.1).1). Although biological function of this remains to be fully unveiled, genetic studies have revealed connection with several phenotypes in various bacterial strains. The disruption llmg1816 gene, which encodes LlYybT by transposon insertion, rendered Lactococcus lactis more tolerant acid stress (28). knockout gcp SmYybT, led abnormal biofilm formation mutans (44). In SA0013 SaYybT, abolished secretion virulence factor hemolysin for iron acquisition, suggesting that SaYybT is crucial vivo survival S. aureus (4). Another study also found deletion seems attenuate during murine infection (2). latest from our laboratory demonstrated ΔBsYybT strain Bacillus subtilis becomes resistant nalidixic acid-caused DNA damage (31). FIG. 1. Domain organization (COG3887). residue numbers shown indicate boundaries BsYybT. The enzymatic activities catalytic domains BsYybT been examined us recently. Among collection potential substrates, C-terminal exhibits phosphodiesterase activity toward cyclic dinucleotides (c)-di-AMP c-di-GMP, micromolar Michaelis-Menten constant (Km) c-di-AMP (31). At moment, however, it not known whether truly physiological substrate despite potent activity. possesses weak ATPase instead diguanylate cyclase (DGC) associated orthodox domains. PAS immediately following second helix prevalent usually comprised five-strand anti-parallel β-sheet four flanking α-helices (17, 40). Many sensor binding ligand cofactors heme, flavin, para-hydroxcinnamate (19, 22, 24, 27, 33). best-characterized include ones bind heme sensing changes oxygen concentration redox state (13, 16, 22). Given low sequence identity shared other characterized domains, little information about can derived sequences. In report, we present results demonstrate able b-type lack apparent residue(s) coordination. heme-bound its thermophilic homolog (GtYybT) their oxidized, reduced, nitric oxide (NO)-, carbon monoxide (CO)-, cyanide (CN−)-ligated forms were absorption spectroscopy. Enzymatic measurement showed affected coordination NO iron. vitro suggest represent unique subfamily heme-binding involved sensing.