THE EVOLUTION OF THE CONSERVED ATPASE DOMAIN (CAD) - RECONSTRUCTING THE HISTORY OF AN ANCIENT PROTEIN MODULE

The AAA proteins (ATPases Associated with a variety of cellular Activi ties) are found in eubacterial, archaebacterial, and eukaryotic specie s and participate in a large number of cellular processes, including p rotein degradation, vesicle fusion, cell cycle control, and cellular s ecretory processes. The AAA proteins are characterized by the presence of a 230 to 250-amino acid ATPase domain referred to as the Conserved ATPase Domain or CAD. Phylogenetic analysis of 133 CAD sequences from 38 species reveal that AAA CADs are organized into discrete groups th at are related not only in structure but in cellular function. Evoluti onary analyses also indicate that the CAD was present in the last comm on ancestor of eubacteria, archaebacteria, and eukaryotes. The eubacte rial CADs are found in metalloproteases, while CAD-containing proteins in the archaebacterial and eukaryotic lineages appear to have diversi fied by a series of gene duplication events that lead to the establish ment of different functional AAA proteins, including proteasomal regul atory, NSF/Sec, and Pas proteins. The phylogeny of the CADs provides t he basis for establishing the patterns of evolutionary change that cha racterize the AAA proteins.