title: Classification of AAA+ proteins.
abstract: 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.
authors.affiliation: Department of Protein Evolution, Max-Planck-Institute for Developmental Biology, D-72076 Tübingen, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Ammelburg
authors.forename: Tancred
authors.initials: T
authors.lastname: Frickey
authors.forename: Andrei N
authors.initials: AN
authors.lastname: Lupas
mesh_terms: D000595:Amino Acid Sequence; D016000:Cluster Analysis; D016208:Databases, Factual; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000145:classification* / Q000235:genetics*
chemical_list: D011506:Proteins