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

Cell. 1999 Jan 8;96(1):99-110. doi: 10.1016/s0092-8674(00)80963-0.


The PR65/A subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit, generating functionally diverse heterotrimers. Mutations of the beta isoform of PR65 are associated with lung and colon tumors. The crystal structure of the PR65/Aalpha subunit, at 2.3 A resolution, reveals the conformation of its 15 tandemly repeated HEAT sequences, degenerate motifs of approximately 39 amino acids present in a variety of proteins, including huntingtin and importin beta. Individual motifs are composed of a pair of antiparallel alpha helices that assemble in a mainly linear, repetitive fashion to form an elongated molecule characterized by a double layer of alpha helices. Left-handed rotations at three interrepeat interfaces generate a novel left-hand superhelical conformation. The protein interaction interface is formed from the intrarepeat turns that are aligned to form a continuous ridge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics
  • Amino Acid Sequence
  • Binding Sites
  • Catalytic Domain
  • Conserved Sequence
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Phosphoprotein Phosphatases / chemistry*
  • Phosphoprotein Phosphatases / genetics
  • Plant Proteins / chemistry*
  • Plant Proteins / genetics
  • Protein Conformation
  • Protein Phosphatase 2
  • Tandem Repeat Sequences*


  • PPP2R1B protein, human
  • Plant Proteins
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2