title: A tryptophan-rich peptide acts as a transcription activation domain.
abstract: BACKGROUND
  Eukaryotic transcription activators normally consist of a sequence-specific DNA-binding domain (DBD) and a transcription activation domain (AD). While many sequence patterns and motifs have been defined for DBDs, ADs do not share easily recognizable motifs or structures.
  
  
  RESULTS
  We report herein that the N-terminal domain of yeast valyl-tRNA synthetase can function as an AD when fused to a DNA-binding protein, LexA, and turn on reporter genes with distinct LexA-responsive promoters. The transcriptional activity was mainly attributed to a five-residue peptide, WYDWW, near the C-terminus of the N domain. Remarkably, the pentapeptide per se retained much of the transcriptional activity. Mutations which substituted tryptophan residues for both of the non-tryptophan residues in the pentapeptide (resulting in W5) significantly enhanced its activity (~1.8-fold), while mutations which substituted aromatic residues with alanine residues severely impaired its activity. Accordingly, a much more active peptide, pentatryptophan (W7), was produced, which elicited ~3-fold higher activity than that of the native pentapeptide and the N domain. Further study indicated that W7 mediates transcription activation through interacting with the general transcription factor, TFIIB.
  
  
  CONCLUSIONS
  Since W7 shares no sequence homology or features with any known transcription activators, it may represent a novel class of AD.
authors.affiliation: Department of Life Science, National Central University, Jung-li 32001, Taiwan.
authors.forename: Chen-Huan
authors.initials: CH
authors.lastname: Lin
authors.forename: Grace
authors.initials: G
authors.lastname: Lin
authors.forename: Chia-Pei
authors.initials: CP
authors.lastname: Chang
authors.forename: Chien-Chia
authors.initials: CC
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D035581:Transcription Factor TFIIB / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014364:Tryptophan / Q000235:genetics* / Q000378:metabolism; D015003:Yeasts / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D010455:Peptides; D012346:RNA, Transfer, Amino Acyl; D011993:Recombinant Fusion Proteins; D035581:Transcription Factor TFIIB; D014364:Tryptophan