Protein phosphatase 1 (PP1) is widely distributed
among tissues and species and acts as a regulator of many
important cellular processes. By targeting the catalytic
part of PP1 (PP1C) toward particular loci and substrates,
regulatory subunits constitute key elements conferring
specificity to the holoenzyme. Here, we report the identification
of an (α/β)8-barrel-like structure within
the N-ter stretch of the human PP1 regulatory subunit hGM,
which is part of the family of diverse proteins associated
with glycogen metabolism. Protein homology modeling gave
rise to a three-dimensional (3D) model for the 381 N-ter
residue stretch of hGM, based on sequence similarity with
Streptomyces olivochromogenes xylose isomerase,
identified by using FASTA. The alignment was subsequently
extended by using hydrophobic cluster analysis. The homology-derived
model includes the putative glycogen binding area located
within the 142–230 domain of hGM as well as a structural
characterization of the PP1C interacting domain (segment
51–67). Refinement of the latter by molecular dynamics
afforded a topology that is in agreement with previous
X-ray studies (Egloff et al., 1997). Finite difference
Poisson–Boltzmann calculations performed on the interacting
domains of PP1C and hGM confirm the complementarity of
the local electrostatic potentials of the two partners.
This work highlights the presence of a conserved fold among
distant species (mammalian, Caenorhabditis elegans,
yeast) and, thus, emphasizes the involvement of PP1 in
crucial basic cellular functions.