The carboxy-terminus, a key regulator of protein function

Area of Science:

• Biochemistry
• Molecular Biology
• Proteomics

Background:

• Proteins terminate with a carboxyl terminus (C-terminus) possessing unique biophysical properties, often disordered.
• While specific C-terminus functions are known, a global role remains underexplored.
• Alternative splicing and proteolysis generate diverse C-termini, expanding cellular protein and peptide variety.

Purpose of the Study:

• To review existing research on the functions of protein C-termini.
• To highlight the significance of C-terminal minimotifs in protein activity.
• To underscore the potential for undiscovered functions within conserved C-terminal motifs.

Main Methods:

• Literature review synthesizing current knowledge on C-termini.
• Analysis of C-terminal minimotifs and their associated functions (binding, posttranslational modifications, trafficking).
• Examination of conserved C-terminal motifs and their presence in databases like TopFIND.

Main Results:

• C-termini contain minimotifs, short functional peptides.
• Approximately 13% of human proteome C-termini possess known minimotifs.
• The majority of C-termini likely harbor undiscovered conserved functional motifs.

Conclusions:

• C-termini are actively exploited by cells for various functions.
• Databases like TopFIND collate C-termini information, aiding functional prediction.
• Further investigation of C-termini is essential for understanding their biochemical and physiological significance in health and disease.