Molecular model of the A subunit of protein phosphatase 2A: interaction with other subunits and tumor antigens.
Protein phosphatase 2A consists of three subunits, the catalytic subunit (C) and two regulatory subunits (A and B). The A subunit has a rod-like shape and consists of 15 nonidentical repeats. It binds the catalytic subunit through repeats 11 to 15 at the C terminus and the tumor antigens encoded by small DNA tumor viruses through overlapping but distinct regions at N-terminal repeats 2 to 8. A model of the A subunit was developed on the basis of the fact that uncharged or hydrophobic amino acids are conserved at eight defined positions within each repeat. Helical wheel projections suggested that each repeat can be arranged as two interacting amphipathic helixes connected by a short loop. Mutational analysis of the A subunit revealed that the proposed loops are important for binding of tumor antigens, the B subunit, and the C subunit. Native gel analysis of mutant A subunits synthesized in vitro demonstrated that the binding region for the B subunit, previously thought to include repeats 2 to 8, covers repeats 1 to 10 and that the B and C subunits cooperate in binding to the A subunit.
Ruediger
R
R
Department of Pathology, University of California at San Diego, La Jolla 92093-0612.
Hentz
M
M
Fait
J
J
Mumby
M
M
Walter
G
G
D000595:Amino Acid Sequence; D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D002474:Cell-Free System; D004252:DNA Mutational Analysis; D046911:Macromolecular Substances; D008958:Models, Molecular; D008961:Models, Structural; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D054648:Protein Phosphatase 2; D017433:Protein Structure, Secondary; D014158:Transcription, Genetic
D000957:Antigens, Viral, Tumor; D046911:Macromolecular Substances; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2