The structure of the protein phosphatase 2A PR65/A subunit reveals the conformation of its 15 tandemly repeated HEAT motifs

The PR65/A subunit of protein phosphatase 2A serves as a scaffolding molecu le to coordinate the assembly of the catalytic subunit and a variable regul atory B subunit, generating functionally diverse heterotrimers. Mutations o f the beta isoform of PR65 are associated with lung and colon tumors. The c rystal structure of the PR65/A alpha subunit, at 2.3 Angstrom resolution, r eveals the conformation of its 15 tandemly repeated HEAT sequences, degener ate motifs of similar to 39 amino acids present in a variety of proteins, i ncluding huntingtin and importin beta. Individual motifs are composed of a pair of antiparallel or helices that assemble in a mainly linear, repetitiv e fashion to form an elongated molecule characterized by a double layer of cw helices. Left-handed rotations at three interrepeat interfaces generate a novel left-hand superhelical conformation. The protein interaction interf ace is formed from the intrarepeat turns that are aligned to form a continu ous ridge.