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 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.
Groves
M R
MR
Department of Biochemistry, University of Oxford, United Kingdom.
Hanlon
N
N
Turowski
P
P
Hemmings
B A
BA
Barford
D
D
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics; D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D017124:Conserved Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000235:genetics; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D054648:Protein Phosphatase 2; D020080:Tandem Repeat Sequences