Eukaryotic protein processing: endoproteolysis of precursor proteins

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Limited endoproteolysis of polypeptide precursors generates diverse biologically active peptides and proteins across eukaryotes.
• A common recognition motif involves cleavage at basic residues (R/K)-Xn-(R/K), found in various protein precursors.

Purpose of the Study:

• To highlight the general mechanism of limited endoproteolysis in generating bioactive peptides.
• To introduce the family of seven mammalian proprotein convertases responsible for this processing.

Main Methods:

• Identification and characterization of seven mammalian proprotein convertase families (PC1/PC3, PC2, furin/PACE, PC4, PACE4, PC5/PC6, PC7/SPC7/LPC/PC8).
• Analysis of the recognition motif for endoproteolytic cleavage at basic residues.

Main Results:

• Seven mammalian proprotein convertases (PCs) have been identified.
• These PCs utilize specific cleavage motifs in precursor proteins.
• The combinatorial action of these PCs dictates the generation of active peptides.

Conclusions:

• Proprotein convertases play a crucial role in processing inactive precursors into active peptides and proteins.
• The cell-type and temporal specificity of PC activity profoundly impacts cellular communication, differentiation, and metabolism.