Profilins, Formins and Katanins as Flagellar Proteins of Leishmania spp.: a Genome-based, Multi-step Bioinformatics-driven Description

Flagellum plays a key role in Leishmania motility and sensory reception, and it is essential for parasite migration, invasion and persistence on host tissues. In search for genomic and/or proteomic evidences of flagellar genes/proteins in Leishmania spp., we have used available databases and computational biology tools to predict and distinguish putative flagellar proteins that are either actin-, tubulin-, axoneme-or microtubule-related sequences and, also, probable virulence factors. Here we present results of sequence and structural analyses of profilins, formins and katanins as possible flagellar proteins of Leishmania spp., whose sequences were in silico selected for predicting viable roles on flagellum assembly, disassembly and dynamics in terms of intraflagellar mechanisms. Taken together, our results provide the first integrated bioinformatics analyses of Leishmania profilin, katanin and formin genes and their gene products to contribute to a more detailed annotation of these important actin-related proteins not yet properly characterized in flagellate trypanosomatids or in their flagellar activities towards virulence.

[1]  Keith Gull,et al.  A "holistic" kinesin phylogeny reveals new kinesin families and predicts protein functions. , 2006, Molecular biology of the cell.

[2]  F. McNally,et al.  A role for katanin-mediated axonemal severing during Chlamydomonas deflagellation. , 1998, Molecular biology of the cell.

[3]  Ian M. Donaldson,et al.  The Biomolecular Interaction Network Database and related tools 2005 update , 2004, Nucleic Acids Res..

[4]  A. Wilkinson,et al.  AAA+ superfamily ATPases: common structure–diverse function , 2001, Genes to cells : devoted to molecular & cellular mechanisms.

[5]  A. Noegel,et al.  Dictyostelium amoebae that lack G-actin-sequestering profilins show defects in F-actin content, cytokinesis, and development , 1994, Cell.

[6]  Yusuke Kato,et al.  Common Mechanism of Ligand Recognition by Group II/III WW Domains , 2004, Journal of Biological Chemistry.

[7]  M. Sudol,et al.  The importance of being proline: the interaction of proline‐rich motifs in signaling proteins with their cognate domains , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  Michely C. Diniz,et al.  Pathogenomics analysis of Leishmania spp.: flagellar gene families of putative virulence factors. , 2005, Omics : a journal of integrative biology.

[9]  N. Morris.  Nuclear migration. From fungi to the mammalian brain. , 2000 .

[10]  P. Bastin,et al.  Novel roles for the flagellum in cell morphogenesis and cytokinesis of trypanosomes , 2003, The EMBO journal.

[11]  M. Ouellette,et al.  A proteomic approach to identify developmentally regulated proteins in Leishmania infantum , 2002, Proteomics.

[12]  W. Haensch,et al.  Tumor suppressor activity of profilin requires a functional actin binding site. , 2004, Molecular biology of the cell.

[13]  J. Thornton,et al.  PROCHECK: a program to check the stereochemical quality of protein structures , 1993 .

[14]  S. Osmani,et al.  NudF, a nuclear migration gene in Aspergillus nidulans, is similar to the human LIS-1 gene required for neuronal migration. , 1995, Molecular biology of the cell.

[15]  A. Sali,et al.  Comparative protein structure modeling of genes and genomes. , 2000, Annual review of biophysics and biomolecular structure.

[16]  R. Valenta,et al.  Profilins constitute a novel family of functional plant pan-allergens , 1992, The Journal of experimental medicine.

[17]  Robert C. Edgar,et al.  MUSCLE: multiple sequence alignment with high accuracy and high throughput. , 2004, Nucleic acids research.

[18]  T. Seebeck,et al.  Identification of a profilin homologue in Trypanosoma brucei by complementation screening. , 1997, Gene.

[19]  M. Quadroni,et al.  Establishing two‐dimensional gels for the analysis of Leishmania proteomes , 2002, Proteomics.

[20]  E V Koonin,et al.  AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. , 1999, Genome research.

[21]  Arnaldo J. Montagner,et al.  STING Millennium Suite: integrated software for extensive analyses of 3d structures of proteins and their complexes , 2004, BMC Bioinformatics.

[22]  Massimo Sassaroli,et al.  Protein Particles in Chlamydomonas Flagella Undergo a Transport Cycle Consisting of Four Phases , 2001, The Journal of cell biology.

[23]  Gongshe Han,et al.  Dynamics of cytoplasmic dynein in living cells and the effect of a mutation in the dynactin complex actin-related protein Arp1 , 2000, Current Biology.

[24]  W. Witke.  The role of profilin complexes in cell motility and other cellular processes. , 2004, Trends in cell biology.

[25]  M. McConville,et al.  Surface determinants of Leishmania parasites and their role in infectivity in the mammalian host. , 2004, Current molecular medicine.

[26]  R. H. Sohn,et al.  Profilin: At the crossroads of signal transduction and the actin cytoskeleton , 1994, BioEssays : news and reviews in molecular, cellular and developmental biology.

[27]  N. Morris,et al.  Cytoplasmic dynein is involved in nuclear migration in Aspergillus nidulans. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Matthew Berriman,et al.  GeneDB: a resource for prokaryotic and eukaryotic organisms , 2004, Nucleic Acids Res..

[29]  T. Blundell,et al.  Comparative protein modelling by satisfaction of spatial restraints. , 1993, Journal of molecular biology.

[30]  K. Hill.  Biology and Mechanism of Trypanosome Cell Motility , 2003, Eukaryotic Cell.

[31]  A. Fedorov,et al.  The molecular basis for allergen cross-reactivity: crystal structure and IgE-epitope mapping of birch pollen profilin. , 1997, Structure.

[32]  K. Thorn,et al.  The crystal structure of a major allergen from plants. , 1997, Structure.

[33]  J. Andersen,et al.  TLR11 Activation of Dendritic Cells by a Protozoan Profilin-Like Protein , 2005, Science.

[34]  A. Valencia,et al.  Molecular and structural analysis of the panallergen profilin B cell epitopes defined by monoclonal antibodies. , 2002, International immunology.

[35]  L. Quarmby,et al.  Chlamydomonas fla mutants reveal a link between deflagellation and intraflagellar transport , 2003, BMC Cell Biology.

[36]  Christophe G. Lambert,et al.  ESyPred3D: Prediction of proteins 3D structures , 2002, Bioinform..

[37]  Richard D Emes,et al.  A new sequence motif linking lissencephaly, Treacher Collins and oral-facial-digital type 1 syndromes, microtubule dynamics and cell migration. , 2001, Human molecular genetics.

[38]  R. Teasdale,et al.  Secretory Pathway of Trypanosomatid Parasites , 2002, Microbiology and Molecular Biology Reviews.

[39]  M. Ouellette,et al.  Proteome Mapping of the Protozoan Parasite Leishmania and Application to the Study of Drug Targets and Resistance Mechanisms* , 2003, Molecular & Cellular Proteomics.

[40]  W. Sale,et al.  Chlamydomonas reinhardtii produces a profilin with unusual biochemical properties. , 2001, Journal of cell science.

[41]  Tetsuya Muramoto,et al.  A comparative sequence analysis reveals a common GBD/FH3-FH1-FH2-DAD architecture in formins from Dictyostelium, fungi and metazoa , 2005, BMC Genomics.

[42]  Steven C. Almo,et al.  Structure of the profilin-poly-L-proline complex involved in morphogenesis and cytoskeletal regulation , 1997, Nature Structural Biology.

[43]  S. Clifton,et al.  A survey of the Leishmania major Friedlin strain V1 genome by shotgun sequencing: a resource for DNA microarrays and expression profiling. , 2001, Molecular and biochemical parasitology.

[44]  Marie-France Carlier,et al.  Formin Is a Processive Motor that Requires Profilin to Accelerate Actin Assembly and Associated ATP Hydrolysis , 2004, Cell.

[45]  K. Miska,et al.  A CONSERVED 19-KDA EIMERIA TENELLA ANTIGEN IS A PROFILIN-LIKE PROTEIN , 2004, The Journal of parasitology.