Structural genomics analysis: Characteristics of atypical, common, and horizontally transferred folds

Hedi Hegyi, Jimmy Lin, Dov Greenbaum, Mark Gerstein

Research output: Contribution to journalArticle

34 Citations (Scopus)


We conducted a structural genomics analysis of the folds and structural superfamilies in the first 20 completely sequenced genomes by focusing on the patterns of fold usage and trying to identify structural characteristics of typical and atypical folds. We assigned folds to sequences using PSI-blast, run with a systematic protocol to reduce the amount of computational overhead. On average, folds could be assigned to about a fourth of the ORFs in the genomes and about a fifth of the amino acids in the proteomes. More than 80% of all the folds in the SCOP structural classification were identified in one of the 20 organisms, with worm and E. coli having the largest number of distinct folds. Folds are particularly effective at comprehensively measuring levels of gene duplication, because they group together even very remote homologues. Using folds, we find the average level of duplication varies depending on the complexity of the organism, ranging from 2.4 in M. genitalium to 32 for the worm, values significantly higher than those observed based purely on sequence similarity. We rank the common folds in the 20 organisms, finding that the top three are the P-loop NTP hydrolase, the ferrodoxin fold, and the TIM-barrel, and discuss in detail the many factors that affect and bias these rankings. We also identify atypical folds that are "unique" to one of the organisms in our study and compare the characteristics of these folds with the most common ones. We find that common folds tend be more multifunctional and associated with more regular, "symmetrical" structures than the unique ones. In addition, many of the unique folds are associated with proteins involved in cell defense (e.g., toxins). We analyze specific patterns of fold occurrence in the genomes by associating some of them with instances of horizontal transfer and others with gene loss. In particular, we find three possible examples of transfer between archaea and bacteria and six between eukarya and bacteria. We make available our detailed results at

Original languageEnglish
Pages (from-to)126-141
Number of pages16
JournalProteins: Structure, Function and Genetics
Issue number2
Publication statusPublished - May 1 2002


ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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