The N-terminal domain influences the structure and property of protein phosphatase 1.

The protein phosphatase 1 has conserved cores in PPP gene family flanked by non-conserved N-terminal domains. PP1 with residues 1–8 deleted or substituted by residues 1–42 of calcineurin catalytic subunit were designated PP1-(9-330) and CNA(1-42)-PP1(9-330), respectively. When compared with PP1, PP1-(9-330) had higher and CNA(1-42)-PP1(9-330) had lower activity with three kinds of substrates; PP1-(9-330) has higher and CNA(1-42)-PP1(9-330) has lower sensitivity to okadaic acid. These results imply that the N-terminal residues influence the activity and sensitivity to inhibitors of PP1. PP1-(9-330), PP1, and CNA(1-42)-PP1(9-330) displayed increasing Km and decreasing Vmax with three kinds of substrates, which suggest that the N-terminal residues are connected with the substrates affinity and catalytic efficiency of PP1. PP1-(9-330) has higher and CNA(1-42)-PP1(9-330) has lower fluorescence intensity than PP1, and the emission wavelength maximum was blue-shifted from PP1 to PP1-(9-330) and red-shifted from PP1 to CNA(1-42)-PP1(9-330). Our findings provide evidence that the N-terminal domain is an important region influencing the structure and properties of PP1.