Comparison of ARM and HEAT protein repeats.

ARM and HEAT motifs are tandemly repeated sequences of approximately 50 amino acid residues that occur in a wide variety of eukaryotic proteins. An exhaustive search of sequence databases detected new family members and revealed that at least 1 in 500 eukaryotic protein sequences contain such repeats. It also rendered the similarity between ARM and HEAT repeats, believed to be evolutionarily related, readily apparent. All the proteins identified in the database searches could be clustered by sequence similarity into four groups: canonical ARM-repeat proteins and three groups of the more divergent HEAT-repeat proteins. This allowed us to build improved sequence profiles for the automatic detection of repeat motifs. Inspection of these profiles indicated that the individual repeat motifs of all four classes share a common set of seven highly conserved hydrophobic residues, which in proteins of known three-dimensional structure are buried within or between repeats. However, the motifs differ at several specific residue positions, suggesting important structural or functional differences among the classes. Our results illustrate that ARM and HEAT-repeat proteins, while having a common phylogenetic origin, have since diverged significantly. We discuss evolutionary scenarios that could account for the great diversity of repeats observed.

[1]  G. Blobel,et al.  Crystallographic Analysis of the Recognition of a Nuclear Localization Signal by the Nuclear Import Factor Karyopherin α , 1998, Cell.

[2]  Dai Hirata,et al.  Identification of Novel Temperature-sensitive Lethal Alleles in Essential β-Tubulin and Nonessential α2-Tubulin Genes as Fission Yeast Polarity Mutants , 1998 .

[3]  A. Goffeau,et al.  II. Yeast sequencing reports. The sequence of a 22·4 kb DNA fragment from the left arm of yeast chromosome II reveals homologues to bacterial proline synthetase and murine α‐adaptin, as well as a new permease and a DNA‐binding protein , 1994 .

[4]  W. Fitch.  Homology a personal view on some of the problems. , 2000, Trends in genetics : TIG.

[5]  Sean R. Eddy,et al.  Profile hidden Markov models , 1998, Bioinform..

[6]  M. Yanagida,et al.  p93dis1, which is required for sister chromatid separation, is a novel microtubule and spindle pole body-associating protein phosphorylated at the Cdc2 target sites. , 1995, Genes & development.

[7]  T. D. Schneider,et al.  Sequence logos: a new way to display consensus sequences. , 1990, Nucleic acids research.

[8]  Jaap Heringa,et al.  The Evolution and Recognition of Protein Sequence Repeats , 1994, Comput. Chem..

[9]  T. Huffaker,et al.  Stu2p: A Microtubule-Binding Protein that Is an Essential Component of the Yeast Spindle Pole Body , 1997, The Journal of cell biology.

[10]  C. Larroque,et al.  The TOGp protein is a new human microtubule-associated protein homologous to the Xenopus XMAP215. , 1998, Journal of cell science.

[11]  W. Franke,et al.  Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[12]  A. Hinnebusch,et al.  Association of GCN1–GCN20 regulatory complex with the N‐terminus of eIF2α kinase GCN2 is required for GCN2 activation , 2000, The EMBO journal.

[13]  T J Gibson,et al.  PairWise and SearchWise: finding the optimal alignment in a simultaneous comparison of a protein profile against all DNA translation frames. , 1996, Nucleic acids research.

[14]  I. Mattaj,et al.  Nucleocytoplasmic transport: the soluble phase. , 1998, Annual review of biochemistry.

[15]  D. Goldfarb,et al.  Evolutionary specialization of the nuclear targeting apparatus. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[16]  K. Kaibuchi,et al.  Purification and characterization from bovine brain cytosol of proteins that regulate the GDP/GTP exchange reaction of smg p21s, ras p21-like GTP-binding proteins. , 1990, The Journal of biological chemistry.

[17]  Rolf Apweiler,et al.  The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000 , 2000, Nucleic Acids Res..

[18]  T. Gibson,et al.  Applying motif and profile searches. , 1996, Methods in enzymology.

[19]  F. Brodsky.  New fashions in vesicle coats. , 1997, Trends in cell biology.

[20]  E. Hartmann,et al.  Isolation of a protein that is essential for the first step of nuclear protein import , 1994, Cell.

[21]  D. Barford,et al.  Topological characteristics of helical repeat proteins. , 1999, Current opinion in structural biology.

[22]  C. Larroque,et al.  Characterization of the cDNA and pattern of expression of a new gene over-expressed in human hepatomas and colonic tumors. , 1995, European journal of biochemistry.

[23]  D. Fremont,et al.  Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[24]  B. Kobe,et al.  Turn up the HEAT. , 1999, Structure.

[25]  M. Frasch,et al.  Pendulin, a Drosophila protein with cell cycle-dependent nuclear localization, is required for normal cell proliferation , 1995, The Journal of cell biology.

[26]  P. Bork,et al.  A Novel Class of RanGTP Binding Proteins , 1997, The Journal of cell biology.

[27]  C. Müller,et al.  Structure of importin-β bound to the IBB domain of importin-α , 1999, Nature.

[28]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[29]  W. Doolittle,et al.  The nature of the universal ancestor and the evolution of the proteome. , 2000, Current opinion in structural biology.

[30]  R. Gräf,et al.  Dictyostelium DdCP224 is a microtubule-associated protein and a permanent centrosomal resident involved in centrosome duplication. , 2000, Journal of cell science.

[31]  R B Russell,et al.  Identification of distant homologues of fibroblast growth factors suggests a common ancestor for all beta-trefoil proteins. , 2000, Journal of molecular biology.

[32]  B. Kobe,et al.  When protein folding is simplified to protein coiling: the continuum of solenoid protein structures. , 2000, Trends in biochemical sciences.

[33]  T. Grigliatti,et al.  A genetic and molecular characterization of the garnet gene of Drosophila melanogaster. , 1999, Genome.

[34]  Peer Bork,et al.  SMART: a web-based tool for the study of genetically mobile domains , 2000, Nucleic Acids Res..

[35]  D. Glover,et al.  mini spindles: A gene encoding a conserved microtubule-associated protein required for the integrity of the mitotic spindle in Drosophila. , 1999 .

[36]  B. Rost,et al.  Protein structures sustain evolutionary drift. , 1997, Folding & design.

[37]  G. Blobel,et al.  Structure of the nuclear transport complex karyopherin-β2–Ran˙GppNHp , 1999, Nature.

[38]  A. Hyman,et al.  Control of microtubule dynamics by the antagonistic activities of XMAP215 and XKCM1 in Xenopus egg extracts , 1999, Nature Cell Biology.

[39]  E. Wieschaus,et al.  Molecular analysis of the armadillo locus: uniformly distributed transcripts and a protein with novel internal repeats are associated with a Drosophila segment polarity gene. , 1989, Genes & development.

[40]  J Kuriyan,et al.  Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha. , 2000, Structure.

[41]  Sven Berg,et al.  A repeating amino acid motif shared by proteins with diverse cellular roles , 1994, Cell.

[42]  J. Deisenhofer,et al.  The leucine-rich repeat: a versatile binding motif. , 1994, Trends in biochemical sciences.

[43]  Brian A. Hemmings,et al.  The Structure of the Protein Phosphatase 2A PR65/A Subunit Reveals the Conformation of Its 15 Tandemly Repeated HEAT Motifs , 1999, Cell.

[44]  Peer Bork,et al.  HEAT repeats in the Huntington's disease protein , 1995, Nature Genetics.

[45]  William I. Weis,et al.  Three-Dimensional Structure of the Armadillo Repeat Region of β-Catenin , 1997, Cell.

[46]  L. Traub.  Clathrin-associated adaptor proteins - putting it all together. , 1997, Trends in cell biology.

[47]  C. Ponting,et al.  Homology-based method for identification of protein repeats using statistical significance estimates. , 2000, Journal of molecular biology.

[48]  A T Brünger,et al.  Sampling and efficiency of metric matrix distance geometry: A novel partial metrization algorithm , 1992, Journal of biomolecular NMR.

[49]  Wei Qian,et al.  Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. , 2000, Molecular biology and evolution.

[50]  S. Emr,et al.  A membrane‐associated complex containing the Vps15 protein kinase and the Vps34 PI 3‐kinase is essential for protein sorting to the yeast lysosome‐like vacuole. , 1993, The EMBO journal.