Diversity in domain architectures of Ser/Thr kinases and their homologues in prokaryotes

Abstract

Background: Ser/Thr/Tyr kinases (STYKs) commonly found in eukaryotes have been recently reported in many bacterial species. Recent studies elucidating their cellular functions have established their roles in bacterial growth and development. However functions of a large number of bacterial STYKs still remain elusive. The organisation of domains in a large dataset of bacterial STYKs has been investigated here in order to recognise variety in domain combinations which determine functions of bacterial STYKs.

Results: Using sensitive sequence and profile search methods, domain organisation of over 600 STYKs from 125 prokaryotic genomes have been examined. Kinase catalytic domains of STYKs tethered to a wide range of enzymatic domains such as phosphatases, HSP70, peptidyl prolyl isomerases, pectin esterases and glycoproteases have been identified. Such distinct preferences for domain combinations are not known to be present in either the Histidine kinase or the eukaryotic STYK families. Domain organisation of STYKs specific to certain groups of bacteria has also been noted in the current anlaysis. For example, Hydrophobin like domains in Mycobacterial STYK and penicillin binding domains in few STYKs of Gram-positive organisms and FHA domains in cyanobacterial STYKs. Homologues of characterised substrates of prokaryotic STYKs have also been identified.

Conclusion: The domains and domain architectures of most of the bacterial STYKs identified are very different from the known domain organisation in STYKs of eukaryotes. This observation highlights distinct biological roles of bacterial STYKs compared to eukaryotic STYKs. Bacterial STYKs reveal high diversity in domain organisation. Some of the modular organisations conserved across diverse bacterial species suggests their central role in bacterial physiology. Unique domain architectures of few other groups of STYKs reveal recruitment of functions specific to the species.

Figure 1

The representative domain combinations of the bacterial homologues of eukaryotic protein kinases are shown. The accession numbers of the protein domain families classified by PFAM are given below. (a) PP2c: phosphatase 2C [PF00481]; (b) Pectinesterase [PF01095]; (c) Glycoprotease [Peptidase_M22; PF00814]; (d) GAF[PF01590], PAS[PF00989], HisK[PF00512], HATPase[PF02518]. (e) FHA: Fork head associated domain [PF00498]; (f) WD-repeats [PF00040]; (g) and (h) amino acid binding domain [ANF_receptor; PF01094]; (i) peptidoglycan binding domain [PASTA, PF03973] k: trans-membrane segment [TM] shown in red.

Figure 2

Multiple sequence alignment of FHA domains seen in bacterial Ser/Thr kinases with the conserved motifs involved in phospho-threonine binding, 'GR', 'SXXH', 'NG' shaded in yellow. gi|17228044|ref|NP_484592.1| (Nostoc sp. PCC 7120), gi|23127167|gb|ZP_00109042.1| (Nostocpunctiforme), gi|22299030|ref|NP_682277.1| (Thermosynechococcus elongatus BP-1), gi|23041283|gb|ZP_00072750.1| (Trichodesmium erythraeum IMS101), gi|22298671|ref|NP_681918.1| (Thermosynechococcus elongatus BP-1) gi|17232446|ref|NP_488994.1| (Nostoc sp. PCC 7120) gi|23043171|gb|ZP_00074493.1| (Trichodesmium erythraeum IMS101) gi|23042923|gb|ZP_00074272.1| (Trichodesmium erythraeum IMS101).

Figure 3

Multiple sequence alignment of the human guanylate cyclase, rat adenylate cyclase and GC-like domain of PKN2 of Myxococcus xanthus is shown. The residues conferring nucleotide specificity are shaded yellow. Conserved hydrophobic and charged residues are shaded green and grey respectively.

Figure 4

Multiple sequence alignment of the activation segment of 'RD' protein kinases in bacteria with the canonical 'DFG', 'APE' shaded in blue and conserved threonines, the potential autophosphorylation sites shaded yellow. gi2911096, gi1370255, gi2131011, gi3261596, gi2131007, gi2078052, (M.tuberculosis); gi13092426 gi13092427 gi13092968 (M.leprae); gi8978468 (C.pneumoniae); gi2633949 (B.subtilis); gi10175124 (B.halodurans); gi12724921 (Lactococcus lactis); gi13622698 (S.pyogenes); gi13701020 gi13701020 (S.aureus); gi6460339 gi6457717 gi6460744 gi6459630 (D.radiodurans); gi13472161 (M.melitoti); gi1652313, gi1006577 gi1653955 gi1653478 gi1652588 (Synechocystis.sp); gi3844698 (M.genitalium); gi1674285 (M.pneumoniae); gi9947763 (P.aeruginosa); gi6899183 (U.ureolyticum).