@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.}
}
Matrix 17023 of 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).
Matrices
Title: Consensus sequences of each ROPK subfamily profile
Rows
Taxon Label |
Row Segments |
Characters 1?–30 |
Sarcocystidae BPK1 |
(none)
|
TTVNVRVPARELVRLLSLTPEQQREGVSAK |
Eucarya sp. ePK |
(none)
|
YELGKVLGSGSFGKVYKARHKDTGEEVAVK |
Sarcocystidae sp. ROP11 |
(none)
|
YTMERILGAGAASIVIQAVQETTRPRVALR |
Sarcocystidae sp. ROP16 |
(none)
|
LYNRGHLGSGHFGAVIKASLDD-GTLYAAK |
Sarcocystidae sp. ROP17 |
(none)
|
LKKRGFLGGGGFGLVYHVEHPTTGQPFALK |
Toxoplasma gondii ROP18 |
(none)
|
LVRGAPLGSGGFATVYEATDVETNEELAVK |
Sarcocystidae sp. ROP19-29-38 |
(none)
|
TGPARFLGMGSTAIVFRLNQVKAPTQVAAK |
Sarcocystidae sp. ROP20 |
(none)
|
FRRGNPLASGSYNVLSEATPVPSSEPVAVR |
Eucoccidiida sp. ROP21-27 |
(none)
|
VIFDGVLGAGGQGVVLLARDVDPGLEMAVK |
Sarcocystidae sp. ROP22 |
(none)
|
LKGIELTGAARGLFVTKVSAVVTKNPLSSS |
Sarcocystidae sp. ROP23 |
(none)
|
ITVKDYIPVAGWGLCVGVVHPESNQEFLLL |
Sarcocystidae sp. ROP24 |
(none)
|
IKYDGILSSGPWSTVLRVMDVDENQEYALK |
Sarcocystidae sp. ROP25 |
(none)
|
AIRGKVLGFGAYGVVVELVDVSRSVTYAAK |
Sarcocystidae sp. ROP26 |
(none)
|
SMRLRPIGIGGTEILLKMRDKQDGGNVPDH |
Sarcocystidae sp. ROP28 |
(none)
|
IIWHKLLGVGGIGGVLLLEDKDPLKKFAGK |
Sarcocystidae sp. ROP2-8 |
(none)
|
LVRGTVLGDDDSYICLEATDQETGESFEVH |
Sarcocystidae sp. ROP30 |
(none)
|
LVAGRLLGGGSEAMVFAAEEIELPRLLAIK |
Sarcocystidae sp. ROP31 |
(none)
|
LTRGELLGCGGTSNVYSMTQED-GTKVAVK |
Sarcocystidae sp. ROP32 |
(none)
|
FVRGPLLGVGGNGLVFEAQDTD-GHVYALK |
Sarcocystidae sp. ROP33 |
(none)
|
MVMLVETPSKELRALVKSAMRALEEPLVVK |
Sarcocystidae sp. ROP34 |
(none)
|
KVTFVDRPSAALLSFLHLEEEDVPYGVVIK |
Eucoccidiida sp. ROP35 |
(none)
|
LVMIVPHVSEALADFLGLDEETREHGIVIK |
Sarcocystidae sp. ROP36 |
(none)
|
IKRLDMINYGYASATYAVKRIFLDQDGALK |
Sarcocystidae sp. ROP37 |
(none)
|
FMRGAFLGAGATGIVTELIEKTSGRYFAAK |
Toxoplasma gondii ROP39 |
(none)
|
LKIRSVAGTGGYNIVVKAFVIKEPQMVSLR |
Eimeria tenella str. Houghton ROP40 |
(none)
|
FERGPMLMTDFFALTVDHQ------PFNMR |
Sarcocystidae sp. ROP41 |
(none)
|
MVRGRYLGVGGNGIVFEASTAHSGESLALK |
Sarcocystidae sp. ROP42-43-44 |
(none)
|
VSLRAPLGIGEYTAVFSGFISGIDSELAVK |
Sarcocystidae sp. ROP45 |
(none)
|
LKRGRFLKYGGGTLLFEVWEGR--KRWGLR |
Sarcocystidae sp. ROP46 |
(none)
|
TLIPVFHMPPQLTADLFSPGESHESGVMVK |
Sarcocystidae sp. ROP47 |
(none)
|
LRMGKVLGGGARSIVVEVMRVDTGDRWALK |
Sarcocystidae sp. ROP4-7 |
(none)
|
LVRGRRIGLFRPGMQFEATDQATGEPMTVL |
Toxoplasma gondii ROP48 |
(none)
|
LYRGPVLGRGTRGIAFKGTMVATGEHFAVK |
Sarcocystidae sp. ROP49 |
(none)
|
LVRGRNVAVTEGAVLFDVTDNESKHEYTAK |
Sarcocystidae sp. ROP5 |
(none)
|
LKLVEPLRVGDRSVVFLVRDVERLEYFALK |
Sarcocystidae sp. ROP50 |
(none)
|
VTRQVYMGSAKLAEDLRVPHALLTGGFTVK |
Eimeria tenella str. Houghton ROPK-Eten1 |
(none)
|
MKVGPALGVGGAGLVLLVEVLSGAKQLAAK |
Eimeria tenella str. Houghton ROPK-Eten2a |
(none)
|
LKIAKFLGEGTFALVLEVKDEETGEVYALR |
Eimeria tenella str. Houghton ROPK-Eten2b |
(none)
|
YEVTRFLGEGLFSLILEVKDKESQRFFALR |
Eimeria tenella str. Houghton ROPK-Eten3 |
(none)
|
VRICKVVGVGFSTLVVEVEDVESGRVYVMH |
Eimeria tenella str. Houghton ROPK-Eten4 |
(none)
|
LKITRIIKFGHSSIFVEVQDVRTYRYVTVR |
Eimeria tenella str. Houghton ROPK-Eten5 |
(none)
|
YTIKRYLYEDNESVTLEIVDQATNLPYAMR |
Eimeria tenella str. Houghton ROPK-Eten6 |
(none)
|
YVVTRFIDQGYQSVLLEVQDRETEGSAAMR |
Columns
None of the columns has a description.