The ribosomal RNA processing 1B:protein phosphatase 1 holoenzyme reveals non-canonical PP1 interaction motifs

Leishmania PNUTS discriminates between PP1 catalytic subunits through a RVxF-ΦΦ-F motif and polymorphisms in the PP1 C-tail and catalytic domain

“…This pocket is also frequently used by other regulators to bind PP1. For example, Gm (F82 GM )(68), spinophilin (T461 spino )(67), and RepoMan/Ki67 (F404 RM )(59) and RRP1B (F696 RRP1B )(61) bind this same pocket. A conserved F118 is present in LtPNUTS and predicted to bind a pocket adjacent to P351 PP1 in the LtPNUTS:PP1 model (Fig.…”

“…Isoform specificity of RRP1B, similar to two other PP1γ-specific regulators (RepoMan and Ki-67), is due to a single amino acid difference in PP1 at position 20, which is an Arg residue in PP1γ/β and a Gln residue in PP1α (64). Structural studies indicated this Arg is part of a hydrophobic AF-binding pocket in PP1, located between the N terminus and the catalytic domain, that engages RRP1B residues 714 AF 715 downstream of the extended RVXF motif, allowing Arg20 to mediate the selectivity of PP1-γ-specific regulators (59, 61). The studies presented here indicate LtPNUTS takes advantage of the divergent extremities of PP1 and novel sequence inserts within the catalytic domain to interact preferentially to the PP1-8e isoform.…”

“…The mammalian PP1 isoforms (PP1a, PP1b, PP1g) share a sequence identity ranging from 85% to 93%, and sequence variability mainly comes from the divergent N- and, most notably, C-termini, with only a few amino acid residues being different within the catalytic domains (2). Among the regulatory PIPs which display isoform preferences, such as MYPT1(56, 57), Spinophilin (58), RepoMan (59), Ki67(59), ASPP2 (60) and RRP1B (61), specificity is achieved via recognition of the PP1 C-terminus or a β/γ specificity pocket within the PP1 catalytic domain. The extreme C-terminus of PP1 (PP1α 309-330 ) contains a SH3-binding motif (PPII –…”

“…Ankyrin repeats of the myosin phosphatase targeting subunit MYPT1 associate with amino acids in the PP1 C-tail and drive selectivity towards PP1β (2). In the case of RRP1B, RepoMan and Ki-67, the SLiM (KiR or SLIV) immediately downstream of the RVxF motif determines the preference toward PP1γ through a single amino acid change in the catalytic domain of PP1(59, 61, 64). Therefore, isoform specificity is mediated in these PIPs by a single amino acid difference in PP1 at position 20, which is an Arg residue in PP1γ/β and a Gln residue in PP1α.…”

Leishmania PNUTS discriminates between PP1 catalytic subunits through an RVxF–ΦΦ–F motif and polymorphisms in the PP1 C-tail and catalytic domain

“…The mammalian PP1 isoforms (PP1α, PP1β, and PP1γ) share a sequence identity ranging from 85% to 93%, and sequence variability mainly comes from the divergent N termini and, most notably, C termini, with only a few amino acid residues being different within the catalytic domains ( 2 ). Among the regulatory RIPPOs, which display isoform preferences, such as MYPT1 ( 65 , 66 ), spinophilin ( 67 ), RepoMan ( 68 ), Ki67 ( 68 ), ASPP2 ( 69 ) and RRP1B ( 70 ), specificity is achieved via recognition of the PP1 C terminus or a β/γ specificity pocket within the PP1 catalytic domain. The extreme C terminus of PP1 (PP1α 309–330 ) contains an SH3-binding motif (PPII–xxPxR), which is conserved among all the mammalian PP1 isoforms, and a variable C-tail.…”