Identification of distant homologues of fibroblast growth factors suggests a common ancestor for all beta-trefoil proteins

C P Ponting, R B Russell

Research output: Contribution to journalArticlepeer-review

Abstract

Determination of the structures of fibroblast growth factors and interleukin-1s has previously revealed that they both adopt a beta-trefoil fold, similar to those found in Kunitz soybean trypsin inhibitors, ricin-like toxins, plant agglutinins and hisactophilin. These families possess distinct functions and occur in different subcellular localisations, and they appear to lack significant similarities in their sequences, ligands and modes of ligand binding. We have analysed the significance of sequence identities observed after structure alignment and provide statistical evidence that these beta-trefoil proteins are all homologues, having arisen from a common ancestor. In addition, we have explored the sequence space of all beta-trefoil proteins and have determined that the actin-binding proteins fascins, and other proteins of unknown function, are beta-trefoil family homologues. Unlike other beta-trefoil proteins, the triplicated repeats in each of the four beta-trefoil domains of fascins are significantly similar in sequence. This hints at how the beta-trefoil fold arose from the duplication of an ancestral gene encoding a homotrimeric single-repeat protein. The combined analysis of structure and sequence databases for detecting significant similarities is suggested as a highly sensitive approach to determining the common ancestry of extremely divergent homologues.

Original languageEnglish
Pages (from-to)1041-7
Number of pages7
JournalJournal of Molecular Biology
Volume302
Issue number5
DOIs
Publication statusPublished - 6 Oct 2000

Keywords

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins
  • Databases, Factual
  • Evolution, Molecular
  • Fibroblast Growth Factors
  • Gene Duplication
  • Genes, Duplicate
  • Humans
  • Microfilament Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Multigene Family
  • Probability
  • Protein Folding
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Sequence Homology

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