High resolution

Module 5: Figure PP2A holoenzyme

Assembly of the protein phosphatase 2A (PP2A) holoenzyme.

The protein phosphatase 2A (PP2A) holoenzyme is assembled from three subunits that have different functions. The molecular framework is provided by the scaffolding subunit (A), which is made up of 15 non-identical repeats, which are organized into a hook-shaped molecule. These repeats are connected by inter-repeat loops (shown in blue). Each repeat has two α-helices that are connected by intra-repeat loops (shown in orange), which line up to provide a cradle to bind the other subunits. Loops 1–10 are responsible for binding one of the regulatory B subunits, which belong to three families (B, B' and B''). There are two PP2A catalytic subunits (Cα and Cβ) and one of these attaches to loops 11–15. This recruitment of the catalytic subunit into the holoenzyme depends upon carboxymethylation of Leu-309 by leucine carboxmethyltransferase (LCMT) and is reversed by a phosphatase methylesterase (PME-1). Once assembled, the holoenzyme functions to dephosphorylate a wide range of phosphorylated substrates.