title: On the origin of the histone fold.
abstract: BACKGROUND
  Histones organize the genomic DNA of eukaryotes into chromatin. The four core histone subunits consist of two consecutive helix-strand-helix motifs and are interleaved into heterodimers with a unique fold. We have searched for the evolutionary origin of this fold using sequence and structure comparisons, based on the hypothesis that folded proteins evolved by combination of an ancestral set of peptides, the antecedent domain segments.
  
  
  RESULTS
  Our results suggest that an antecedent domain segment, corresponding to one helix-strand-helix motif, gave rise divergently to the N-terminal substrate recognition domain of Clp/Hsp100 proteins and to the helical part of the extended ATPase domain found in AAA+ proteins. The histone fold arose subsequently from the latter through a 3D domain-swapping event. To our knowledge, this is the first example of a genetically fixed 3D domain swap that led to the emergence of a protein family with novel properties, establishing domain swapping as a mechanism for protein evolution.
  
  
  CONCLUSIONS
  The helix-strand-helix motif common to these three folds provides support for our theory of an 'ancient peptide world' by demonstrating how an ancestral fragment can give rise to 3 different folds.
authors: Department of Protein Evolution, Max-Planck-Institute for Developmental Biology, Tübingen, Germany. vikram.alva@tuebingen.mpg.de <vikram.alva@tuebingen.mpg.de>
authors: Vikram
authors: V
authors: Alva
authors: Moritz
authors: M
authors: Ammelburg
authors: Johannes
authors: J
authors: Söding
authors: Andrei N
authors: AN
authors: Lupas
mesh_terms: D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D030562:Databases, Protein; D019143:Evolution, Molecular; D006657:Histones / Q000737:chemistry* / Q000235:genetics*; D017510:Protein Folding; D017434:Protein Structure, Tertiary / Q000235:genetics; D040681:Structural Homology, Protein
chemical_list: D019843:Archaeal Proteins; D001426:Bacterial Proteins; D006657:Histones