Identification and phylogenetic analyses of VASt, an uncharacterized protein domain associated with lipid-binding domains in Eukaryotes

BackgroundSeveral regulators of programmed cell death (PCD) in plants encode proteins with putative lipid-binding domains. Among them, VAD1 is a regulator of PCD propagation harboring a GRAM putative lipid-binding domain. However the function of VAD1 at the subcellular level is unknown and the domain architecture of VAD1 has not been analyzed in details.ResultsWe analyzed sequence conservation across the plant kingdom in the VAD1 protein and identified an uncharacterized VASt (VAD1 Analog of StAR-related lipid transfer) domain. Using profile hidden Markov models (profile HMMs) and phylogenetic analysis we found that this domain is conserved among eukaryotes and generally associates with various lipid-binding domains. Proteins containing both a GRAM and a VASt domain include notably the yeast Ysp2 cell death regulator and numerous uncharacterized proteins. Using structure-based phylogeny, we found that the VASt domain is structurally related to Bet v1-like domains.ConclusionWe identified a novel protein domain ubiquitous in Eukaryotic genomes and belonging to the Bet v1-like superfamily. Our findings open perspectives for the functional analysis of VASt-containing proteins and the characterization of novel mechanisms regulating PCD.

[1]  Y. Fujita,et al.  Structure and function of abscisic acid receptors. , 2013, Trends in plant science.

[2]  Adam Godzik,et al.  Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences , 2006, Bioinform..

[3]  Yasuyoshi Sakai,et al.  PI4P-signaling pathway for the synthesis of a nascent membrane structure in selective autophagy , 2006, The Journal of cell biology.

[4]  Erik L. L. Sonnhammer,et al.  Predicting protein function from domain content , 2008, Bioinform..

[5]  D. Roby,et al.  Lesion mimic mutants: keys for deciphering cell death and defense pathways in plants? , 2003, Trends in plant science.

[6]  Toni Gabaldón,et al.  trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses , 2009, Bioinform..

[7]  K. Katoh,et al.  MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. , 2002, Nucleic acids research.

[8]  M. Degano,et al.  Crystal structure of a hypoallergenic isoform of the major birch pollen allergen Bet v 1 and its likely biological function as a plant steroid carrier. , 2003, Journal of molecular biology.

[9]  P. Bork,et al.  GRAM, a novel domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins. , 2000, Trends in biochemical sciences.

[10]  N. Ban,et al.  Membrane association of myotubularin-related protein 2 is mediated by a pleckstrin homology-GRAM domain and a coiled-coil dimerization module , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D. Klessig,et al.  A fatty acid desaturase modulates the activation of defense signaling pathways in plants , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[12]  E. Koonin,et al.  Adaptations of the helix‐grip fold for ligand binding and catalysis in the START domain superfamily , 2001, Proteins.

[13]  K. Ehlers,et al.  Developmental Control of Plasmodesmata Frequency, Structure, and Function , 2013 .

[14]  Yang Zhang,et al.  I-TASSER server for protein 3D structure prediction , 2008, BMC Bioinformatics.

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

[16]  J. Song,et al.  Ceramides modulate programmed cell death in plants. , 2003, Genes & development.

[17]  Artemis Perraki,et al.  Plasma Membrane Localization of Solanum tuberosum Remorin from Group 1, Homolog 3 Is Mediated by Conformational Changes in a Novel C-Terminal Anchor and Required for the Restriction of Potato Virus X Movement1[C][W] , 2012, Plant Physiology.

[18]  A. Hyman,et al.  Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast , 2005, The Journal of cell biology.

[19]  T. Takenawa,et al.  Myotubularin Regulates the Function of the Late Endosome through the GRAM Domain-Phosphatidylinositol 3,5-Bisphosphate Interaction* , 2004, Journal of Biological Chemistry.

[20]  Jörg Schultz,et al.  HMM Logos for visualization of protein families , 2004, BMC Bioinformatics.

[21]  M. Jaskólski,et al.  Structural and functional aspects of PR‐10 proteins , 2013, The FEBS journal.

[22]  K. Hanada,et al.  Interorganelle Trafficking of Ceramide Is Regulated by Phosphorylation-dependent Cooperativity between the PH and START Domains of CERT* , 2007, Journal of Biological Chemistry.

[23]  D. Roby,et al.  VASCULAR ASSOCIATED DEATH1, a Novel GRAM Domain–Containing Protein, Is a Regulator of Cell Death and Defense Responses in Vascular Tissues , 2004, The Plant Cell Online.

[24]  S. Ramachandran,et al.  Comparative transcriptional profiling and evolutionary analysis of the GRAM domain family in eukaryotes. , 2008, Developmental biology.

[25]  P. Sowiński,et al.  Symplasmic Transport in Vascular Plants , 2013, Springer New York.

[26]  O. Gascuel,et al.  New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. , 2010, Systematic biology.

[27]  S. Lev.  Non-vesicular lipid transport by lipid-transfer proteins and beyond , 2010, Nature Reviews Molecular Cell Biology.

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

[29]  V. Skulachev,et al.  Ysp2 mediates death of yeast induced by amiodarone or intracellular acidification. , 2006, Biochimica et biophysica acta.

[30]  Hong-Gang Wang,et al.  Sphingolipids: regulators of crosstalk between apoptosis and autophagy , 2013, Journal of Lipid Research.

[31]  S. Teichmann,et al.  Supra-domains: evolutionary units larger than single protein domains. , 2004, Journal of molecular biology.

[32]  Robert D. Finn,et al.  HMMER web server: interactive sequence similarity searching , 2011, Nucleic Acids Res..

[33]  L. Torrance,et al.  Plasmodesmata viewed as specialised membrane adhesion sites , 2010, Protoplasma.

[34]  E. Birney,et al.  Pfam: the protein families database , 2013, Nucleic Acids Res..

[35]  Guy Pratt,et al.  A genome-wide association study identifies six susceptibility loci for chronic lymphocytic leukemia , 2008, Nature Genetics.

[36]  Peter J. Stuckey,et al.  MUSTANG-MR Structural Sieving Server: Applications in Protein Structural Analysis and Crystallography , 2010, PloS one.

[37]  Yang Zhang,et al.  I-TASSER: a unified platform for automated protein structure and function prediction , 2010, Nature Protocols.

[38]  P. Lackner,et al.  The Bet v 1 fold: an ancient, versatile scaffold for binding of large, hydrophobic ligands , 2008, BMC Evolutionary Biology.

[39]  J. Mundy,et al.  Knockout of Arabidopsis accelerated-cell-death11 encoding a sphingosine transfer protein causes activation of programmed cell death and defense. , 2002, Genes & development.

[40]  M. Knutson,et al.  Fine-Mapping and Genetic Analysis of the Loci Affecting Hepatic Iron Overload in Mice , 2013, PloS one.

[41]  D. Roby,et al.  Ethylene Is One of the Key Elements for Cell Death and Defense Response Control in the Arabidopsis Lesion Mimic Mutant vad11[W] , 2007, Plant Physiology.

[42]  C. Chothia,et al.  Evolution of the Protein Repertoire , 2003, Science.

[43]  Conrad C. Huang,et al.  UCSF Chimera—A visualization system for exploratory research and analysis , 2004, J. Comput. Chem..

[44]  Eun-Jeong Lee,et al.  Norcoclaurine Synthase Is a Member of the Pathogenesis-Related 10/Bet v1 Protein Family[W] , 2010, Plant Cell.

[45]  David Posada,et al.  ProtTest: selection of best-fit models of protein evolution , 2005, Bioinform..

[46]  T. Dunn,et al.  An Inositolphosphorylceramide Synthase Is Involved in Regulation of Plant Programmed Cell Death Associated with Defense in Arabidopsis[C][W] , 2008, The Plant Cell Online.

[47]  Prahlad T. Ram,et al.  2′-OMe-phosphorodithioate-modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity , 2014, Nature Communications.

[48]  J. Söding,et al.  More than the sum of their parts: On the evolution of proteins from peptides , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[49]  Peer Bork,et al.  Interactive Tree Of Life v2: online annotation and display of phylogenetic trees made easy , 2011, Nucleic Acids Res..

[50]  C. Tomasetto,et al.  Give lipids a START: the StAR-related lipid transfer (START) domain in mammals , 2005, Journal of Cell Science.

[51]  S. Xiao,et al.  Sphingolipids and Plant Defense/Disease: The “Death” Connection and Beyond , 2012, Front. Plant Sci..

[52]  D. Tang,et al.  Regulation of plant defense responses in Arabidopsis by EDR2, a PH and START domain-containing protein. , 2005, The Plant journal : for cell and molecular biology.

[53]  M. P. Cummings.  PHYLIP (Phylogeny Inference Package) , 2004 .

[54]  M. Nishimura,et al.  EDR2 negatively regulates salicylic acid-based defenses and cell death during powdery mildew infections of Arabidopsis thaliana , 2007, BMC Plant Biology.

[55]  W. Moeder,et al.  Lesion mimic mutants , 2008, Plant signaling & behavior.

[56]  Geoffrey J. Barton,et al.  Protein sequence alignments: a strategy for the hierarchical analysis of residue conservation , 1993, Comput. Appl. Biosci..

[57]  B. Sjöberg,et al.  Use of Structural Phylogenetic Networks for Classification of the Ferritin-like Superfamily* , 2012, The Journal of Biological Chemistry.