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Citation for Study 14212

Citation title: "Structural and evolutionary adaptation of rhoptry kinases and pseudokinases, a family of coccidian virulence factors".

Study name: "Structural and evolutionary adaptation of rhoptry kinases and pseudokinases, a family of coccidian virulence factors".

This study is part of submission 14212 (Status: Published).

Citation

Talevich E., & Kannan N. 2013. Structural and evolutionary adaptation of rhoptry kinases and pseudokinases, a family of coccidian virulence factors. BMC Evolutionary Biology, 13: 117.

Authors

• Talevich E. (submitter)
• Kannan N.

Abstract

BACKGROUND: The widespread protozoan parasite Toxoplasma gondii interferes with host cell functions by exporting the contents of a unique apical organelle, the rhoptry. Among the mix of secreted proteins are an expanded, lineage-specific family of protein kinases termed rhoptry kinases (ROPKs), several of which have been shown to be key virulence factors, including the pseudokinase ROP5. The extent and details of the diversification of this protein family are poorly understood. RESULTS: In this study, we comprehensively catalogued the ROPK family in the genomes of Toxoplasma gondii, Neospora caninum and Eimeria tenella, as well as portions of the unfinished genome of Sarcocystis neurona, and classified the identified genes into 41 distinct subfamilies. We systematically compared the rhoptry kinase protein sequences and structures to each other and to the broader superfamily of eukaryotic protein kinases to study the patterns of diversification and neofunctionalization in the ROPK family and its subfamilies. We identified three ROPK sub-clades of particular interest: those bearing a structurally conserved N-terminal extension to the kinase domain (NTE), an E. tenella-specific expansion, and a basal cluster including ROP35 and BPK1 that we term ROPKL. Structural analysis in light of the solved structures ROP2, ROP5, ROP8 and in comparison to typical eukaryotic 1protein kinases revealed ROPK-specific conservation patterns in two key regions of the kinase domain, surrounding a ROPK-conserved insert in the kinase hinge region and a disulfide bridge in the kinase substrate-binding lobe. We also examined conservation patterns specific to the NTE-bearing clade. We discuss the possible functional consequences of each. CONCLUSIONS: Our work sheds light on several important but previously unrecognized features shared among rhoptry kinases, as well as the essential differences between active and degenerate protein kinases. We identify the most distinctive ROPK-specific features conserved across both active kinases and pseudokinases, and discuss these in terms of sequence motifs, evolutionary context, structural impact and potential functional relevance. By characterizing the proteins that enable these parasites to invade the host cell and co-opt its signaling mechanisms, we provide guidance on potential therapeutic targets for the diseases caused by coccidian parasites.

Keywords

host-pathogen interaction; protein kinase; pseudokinase; toxoplasma

External links

• DOI: 10.1186/1471-2148-13-117
• Other URL: http://www.biomedcentral.com/1471-2148/13/117

About this resource

• Canonical resource URI: http://purl.org/phylo/treebase/phylows/study/TB2:S14212
• Other versions: Nexus NeXML
• Show BibTeX reference

  		@ARTICLE{TreeBASE2Ref21982,
  	 author = {Eric  Talevich and Natarajan  Kannan},
  	 title = {Structural and evolutionary adaptation of rhoptry kinases and pseudokinases, a family of coccidian virulence factors},
  	 year = {2013},
  	 keywords = {host-pathogen interaction; protein kinase; pseudokinase; toxoplasma},
  	 doi = {10.1186/1471-2148-13-117},
  	 url = {http://www.biomedcentral.com/1471-2148/13/117},
  	 pmid = {},
  	 journal = {BMC Evolutionary Biology},
  	 volume = {13},
  	 number = {},
  	 pages = {117},
  	 abstract = {BACKGROUND: The widespread protozoan parasite Toxoplasma gondii interferes with host cell functions by exporting the contents
  of a unique apical organelle, the rhoptry. Among the mix of secreted proteins are an expanded, lineage-specific
  family of protein kinases termed rhoptry kinases (ROPKs), several of which have been shown to be key virulence
  factors, including the pseudokinase ROP5. The extent and details of the diversification of this protein family are
  poorly understood.
  
  RESULTS: In this study, we comprehensively catalogued the ROPK family in the genomes of Toxoplasma gondii, Neospora
  caninum and Eimeria tenella, as well as portions of the unfinished genome of Sarcocystis neurona, and classified
  the identified genes into 41 distinct subfamilies. We systematically compared the rhoptry kinase protein sequences
  and structures to each other and to the broader superfamily of eukaryotic protein kinases to study the patterns
  of diversification and neofunctionalization in the ROPK family and its subfamilies. We identified three ROPK
  sub-clades of particular interest: those bearing a structurally conserved N-terminal extension to the kinase domain
  (NTE), an E. tenella-specific expansion, and a basal cluster including ROP35 and BPK1 that we term ROPKL.
  Structural analysis in light of the solved structures ROP2, ROP5, ROP8 and in comparison to typical eukaryotic
  1protein kinases revealed ROPK-specific conservation patterns in two key regions of the kinase domain, surrounding
  a ROPK-conserved insert in the kinase hinge region and a disulfide bridge in the kinase substrate-binding lobe.
  We also examined conservation patterns specific to the NTE-bearing clade. We discuss the possible functional
  consequences of each.
  
  CONCLUSIONS: Our work sheds light on several important but previously unrecognized features shared among rhoptry kinases, as
  well as the essential differences between active and degenerate protein kinases. We identify the most distinctive
  ROPK-specific features conserved across both active kinases and pseudokinases, and discuss these in terms of
  sequence motifs, evolutionary context, structural impact and potential functional relevance. By characterizing
  the proteins that enable these parasites to invade the host cell and co-opt its signaling mechanisms, we provide
  guidance on potential therapeutic targets for the diseases caused by coccidian parasites.}
  }
  		

• Show RIS reference

  		TY  - JOUR
  ID  - 21982
  AU  - Talevich,Eric 
  AU  - Kannan,Natarajan 
  T1  - Structural and evolutionary adaptation of rhoptry kinases and pseudokinases, a family of coccidian virulence factors
  PY  - 2013
  KW  - host-pathogen interaction; protein kinase; pseudokinase; toxoplasma
  UR  - http://www.biomedcentral.com/1471-2148/13/117
  N2  - BACKGROUND: The widespread protozoan parasite Toxoplasma gondii interferes with host cell functions by exporting the contents
  of a unique apical organelle, the rhoptry. Among the mix of secreted proteins are an expanded, lineage-specific
  family of protein kinases termed rhoptry kinases (ROPKs), several of which have been shown to be key virulence
  factors, including the pseudokinase ROP5. The extent and details of the diversification of this protein family are
  poorly understood.
  
  RESULTS: In this study, we comprehensively catalogued the ROPK family in the genomes of Toxoplasma gondii, Neospora
  caninum and Eimeria tenella, as well as portions of the unfinished genome of Sarcocystis neurona, and classified
  the identified genes into 41 distinct subfamilies. We systematically compared the rhoptry kinase protein sequences
  and structures to each other and to the broader superfamily of eukaryotic protein kinases to study the patterns
  of diversification and neofunctionalization in the ROPK family and its subfamilies. We identified three ROPK
  sub-clades of particular interest: those bearing a structurally conserved N-terminal extension to the kinase domain
  (NTE), an E. tenella-specific expansion, and a basal cluster including ROP35 and BPK1 that we term ROPKL.
  Structural analysis in light of the solved structures ROP2, ROP5, ROP8 and in comparison to typical eukaryotic
  1protein kinases revealed ROPK-specific conservation patterns in two key regions of the kinase domain, surrounding
  a ROPK-conserved insert in the kinase hinge region and a disulfide bridge in the kinase substrate-binding lobe.
  We also examined conservation patterns specific to the NTE-bearing clade. We discuss the possible functional
  consequences of each.
  
  CONCLUSIONS: Our work sheds light on several important but previously unrecognized features shared among rhoptry kinases, as
  well as the essential differences between active and degenerate protein kinases. We identify the most distinctive
  ROPK-specific features conserved across both active kinases and pseudokinases, and discuss these in terms of
  sequence motifs, evolutionary context, structural impact and potential functional relevance. By characterizing
  the proteins that enable these parasites to invade the host cell and co-opt its signaling mechanisms, we provide
  guidance on potential therapeutic targets for the diseases caused by coccidian parasites.
  L3  - 10.1186/1471-2148-13-117
  JF  - BMC Evolutionary Biology
  VL  - 13
  IS  - 
  ER  -