title: NleH defines a new family of bacterial effector kinases.
abstract: Upon host cell infection, pathogenic Escherichia coli hijacks host cellular processes with the help of 20-60 secreted effector proteins that subvert cellular processes to create an environment conducive to bacterial survival. The NleH effector kinases manipulate the NF-κB pathway and prevent apoptosis. They show low sequence similarity to human regulatory kinases and contain two domains, the N-terminal, likely intrinsically unfolded, and a C-terminal kinase-like domain. We show that these effectors autophosphorylate on sites located predominantly in the N-terminal segment. The kinase domain displays a minimal kinase fold, but lacks an activation loop and the GHI subdomain. Nevertheless, all catalytically important residues are conserved. ATP binding proceeds with minimal structural rearrangements. The NleH structure is the first for the bacterial effector kinases family. NleHs and their homologous effector kinases form a new kinase family within the cluster of eukaryotic-like kinases that includes also Rio, Bud32, and KdoK families.
authors.affiliation: Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada. Electronic address: andrey.grishin@usask.ca.
authors.forename: Andrey M
authors.initials: AM
authors.lastname: Grishin
authors.affiliation: Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
authors.forename: Maia
authors.initials: M
authors.lastname: Cherney
authors.affiliation: Cancer Research, Saskatchewan Cancer Agency, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada.
authors.forename: Deborah H
authors.initials: DH
authors.lastname: Anderson
authors.affiliation: Department of Biochemistry, Research and Innovation Centre, University of Regina, 3737 Wascana Parkway, Regina, SK S4S 0A2, Canada.
authors.forename: Sadhna
authors.initials: S
authors.lastname: Phanse
authors.affiliation: Department of Biochemistry, Research and Innovation Centre, University of Regina, 3737 Wascana Parkway, Regina, SK S4S 0A2, Canada.
authors.forename: Mohan
authors.initials: M
authors.lastname: Babu
authors.affiliation: Department of Biochemistry, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK S7N 5E5, Canada; Department of Biochemistry, McGill University, 3655 Promenade Sir Willam Osler, Montreal, QC H3G 1Y6, Canada. Electronic address: miroslaw.cygler@usask.ca.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Cygler
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000595:Amino Acid Sequence; D017209:Apoptosis; D002384:Catalysis; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000737:chemistry; D010766:Phosphorylation; D010770:Phosphotransferases / Q000737:chemistry*; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
chemical_list: D029968:Escherichia coli Proteins; D016328:NF-kappa B; C556114:NleH protein, E coli; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D010770:Phosphotransferases