AlphaFold-Multimer (v3) model of a complex of Protein Phosphatase 2A catalytic subunit (PP2A/C), PP2A scaffold subunit (PP2A/A), the B55alpha substrate binding subunit, and FAM122A, a PP2A inhibitor protein.

AlphaFold-Multimer (v3) model structure of a complex of Protein Phosphatase 2A catalytic subunit (PP2A/C), PP2A scaffold subunit (PP2A/A), the B55alpha substrate binding subunit, and FAM122A, a PP2A inhibitor protein. The protein sequences were obtained from UniProt:

P67775 · PP2AA_HUMAN

P30153 · 2AAA_HUMAN

P63151 · 2ABA_HUMAN

Q96E09 · PBIR1_HUMAN

Coordinates are in mmCIF format. A PyMOL session file is included.

Modeling was performed with AlphaFold-Multimer v3, downloaded from DeepMind's github. Structure prediction was performed without templates. The model was relaxed with Amber.

FAM122A binds using a short linear motif (SLIM) (residues 84-89) first identified in RBL1 (p107) (Fowle et al., eLife, https://doi.org/10.7554/eLife.63181 in the form of a short alpha helix (residues 84-92). This is followed by a long alpha helix (residues 96-122) which blocks access to the active site of the catalytic subunit. There are further contacts of FAM122A (residues 150-170) with one of the beta sheets of the B55alpha beta propeller domain. FAM122A regulates PP2A activity during the cell cycle.