ABSTRACT
Background Helical repeat motifs such as ANK, HEAT, and ARM are thought to primarily mediate protein-protein interactions (see reviews[1-3]). Helical repeat motifs are a recurrent theme among regulatory subunits for dierent protein Ser/r phosphatases. Best studied is the A or PR65 subunit of PP2A, an all-helical subunit rst designated to consist of Armadillo (ARM) sequence repeats, that were later called HEAT repeats [4], a name derived from proteins with related sequence motifs: Huntingtin’s, elongation factor, A subunit of PP2A and TOR. e 3D structure of the A subunit of PP2A alone [5], as a dimer bound to the PP2A catalytic subunit [6], and as a scaold to assemble PP2A heterotrimers [7-9], showed the all-helical organization and revealed dierences in overall conformation due to association with the other subunits. e extended arc of helices is shaped like a banana in the monomer or heterodimer and closes to a horseshoe-shaped
conformation in the heterotrimer. In addition, in the ABC trimers the regulatory B’56 subunit of PP2A was found to be a HEAT-like helical repeat protein that contacts both the A and C subunits. e structure of B’56 was unexpected because it was not predicted based on sequence alignments with other HEATrepeat proteins. Another example of helical repeat motifs in protein phosphatase subunits is the MYPT1 subunit for PP1, with 8 ankyrin repeats [10]. In the 3D structure these repeats form an arc of alpha helices to engage the top surface of the PP1 catalytic subunit and enwrap the C-terminal tail that protrudes from the top surface of the subunit. Both the ANK repeats as well as a separate structural element consisting of an alpha helix plus a neighboring strand with the canonical RVxF motif make contacts with the PP1 catalytic subunit. Based on these examples there is the expectation that other phosphatase regulatory subunits might be comprised of helical repeat structures and use these repeats to mediate subunitsubunit association.
