Classification of AAA+ Proteins

J Struct Biol. 2006 Oct;156(1):2-11. doi: 10.1016/j.jsb.2006.05.002. Epub 2006 May 26.


AAA+ proteins form a large superfamily of P-loop ATPases involved in the energy-dependent unfolding and disaggregation of macromolecules. In a clustering study aimed at defining the AAA proteins within this superfamily, we generated a map of AAA+ proteins based on sequence similarity, which suggested higher-order groups. A classification based primarily on morphological characteristics, which was proposed at the same time, differed from the cluster map in several aspects, such as the position of RuvB-like helicases and the inclusion of divergent clades, such as viral SF3 helicases and plant disease resistance proteins (RFL1). Here, we establish the presence of an alpha-helical domain C-terminal to the ATPase domain (the C-domain) as characteristic for AAA+ proteins and re-evaluate all clades proposed to belong to this superfamily, based on this characteristic. We find that RFL1 and its homologs (APAF-1, CED-4, MalT, and AfsR) are AAA+ proteins and SF3 helicases are not. We also present a new and more comprehensive cluster map, which assigns a central position to RuvB and clarifies the relationships between the clades of the AAA+ superfamily.

MeSH terms

  • Amino Acid Sequence*
  • Cluster Analysis
  • Databases, Factual
  • Evolution, Molecular
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Proteins / classification*
  • Proteins / genetics*


  • Proteins