Type III effector NleH2 from Escherichia coli O157:H7 str. Sakai features an atypical protein kinase domain.

The crystal structure of a C-terminal domain of enterohemorrhagic Escherichia coli type III effector NleH2 has been determined to 2.6 Å resolution. The structure resembles those of protein kinases featuring the catalytic, activation, and glycine-rich loop motifs and ATP-binding site. The position of helix αC and the lack of a conserved arginine within an equivalent HRD motif suggested that the NleH2 kinase domain's active conformation might not require phosphorylation. The activation segment markedly contributed to the dimerization interface of NleH2, which can also accommodate the NleH1-NleH2 heterodimer. The C-terminal PDZ-binding motif of NleH2 provided bases for interaction with host proteins.

[1]  J. Villén,et al.  E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis , 2014, The EMBO journal.

[2]  S. Sheng,et al.  Structural Insights into Neutrophilic Migration Revealed by the Crystal Structure of the Chemokine Receptor CXCR2 in Complex with the First PDZ Domain of NHERF1 , 2013, PloS one.

[3]  Mingjie Zhang,et al.  Structures and target recognition modes of PDZ domains: recurring themes and emerging pictures. , 2013, The Biochemical journal.

[4]  Yan Zhou,et al.  The Shigella Type Three Secretion System Effector OspG Directly and Specifically Binds to Host Ubiquitin for Activation , 2013, PloS one.

[5]  Patrick R. Cushing,et al.  Stereochemical Determinants of C-terminal Specificity in PDZ Peptide-binding Domains , 2012, The Journal of Biological Chemistry.

[6]  Susan S. Taylor,et al.  Evolution of the eukaryotic protein kinases as dynamic molecular switches , 2012, Philosophical Transactions of the Royal Society B: Biological Sciences.

[7]  F. Wan,et al.  Functional Differences and Interactions between the Escherichia coli Type III Secretion System Effectors NleH1 and NleH2 , 2012, Infection and Immunity.

[8]  Cecilia S. Lindestam Arlehamn,et al.  Expression and Regulation of the Escherichia coli O157:H7 Effector Proteins NleH1 and NleH2 , 2012, PloS one.

[9]  Virgil L. Woods,et al.  A conserved Glu-Arg salt bridge connects coevolved motifs that define the eukaryotic protein kinase fold. , 2012, Journal of molecular biology.

[10]  J. Pearson,et al.  Enteropathogenic and enterohaemorrhagic Escherichia coli: even more subversive elements , 2011, Molecular microbiology.

[11]  J. Turner,et al.  Enteropathogenic E. coli non‐LEE encoded effectors NleH1 and NleH2 attenuate NF‐κB activation , 2010, Molecular microbiology.

[12]  E. Martinez,et al.  Binding to Na+/H+ exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH , 2010, Cellular microbiology.

[13]  Jie J. Zheng,et al.  ReviewPDZ domains and their binding partners : structure , specificity , and modification , 2010 .

[14]  A. Mousnier,et al.  NleH effectors interact with Bax inhibitor-1 to block apoptosis during enteropathogenic Escherichia coli infection , 2010, Proceedings of the National Academy of Sciences.

[15]  B. Finlay,et al.  Bacterial Effector Binding to Ribosomal Protein S3 Subverts NF-κB Function , 2009, PLoS pathogens.

[16]  M. Tortorici,et al.  Crystal structure of the catalytic domain of Haspin, an atypical kinase implicated in chromatin organization , 2009, Proceedings of the National Academy of Sciences.

[17]  Susan S. Taylor,et al.  Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism , 2006, Proceedings of the National Academy of Sciences.

[18]  H. Jäckle,et al.  Mitogen‐activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment , 2006, The EMBO journal.

[19]  Nicolas Foloppe,et al.  Identification of a buried pocket for potent and selective inhibition of Chk1: prediction and verification. , 2005, Bioorganic & medicinal chemistry.

[20]  Pierre Legrain,et al.  The Shigella flexneri effector OspG interferes with innate immune responses by targeting ubiquitin-conjugating enzymes. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J F Gibrat,et al.  Surprising similarities in structure comparison. , 1996, Current opinion in structural biology.

[22]  G. Wu,et al.  Structures of bis(2-methoxyethylcyclopentadienyl) complexes of lanthanide chlorides , 1993 .

[23]  Susan S. Taylor,et al.  A template for the protein kinase family. , 1993, Trends in biochemical sciences.