Terminal Modifications

Modifications of N- & C-termini

Overview

PROTEIN MODIFICATION

Amino acid residues may be modified co-translationally or post-translationally
Amino or carboxy termini of polypeptide chain can be modified post-translationally

Limitations of this tutorial

We will only represent some of the many ways that amino acid residues can be modified.
No single protein will have the number of modifications that we show here.

N-TERMINAL MODIFICATIONS

N-terminal acetylation: increases protein stability (resistance to degradation)
Varshavsky's N-end rule: N-terminal amino acid determines protein's likelihood of being degraded --> N-terminal amino acid estimates protein half-life (N-terminal amino acid modifications introduce variability)

N-terminal signal sequences: localization signals; protein targeted to organelle

C-TERMINAL MODIFICATION

GPI (glycosyl phosphatidylinositol) anchor: C-terminus glycolipid targets/anchors protein to plasma membrane

(membrane anchors ~ most common C-term. modification)

C-terminal signal peptide: localization (e.g. KDEL sequence: targets polypeptide chain back to ER from Golgi)

PEPTIDE CLEAVAGE

Proteins synthesized in inactive precursor form (pro-proteins or pro-peptides)
Regulates enzyme activity (i.e. proteases)
Proteins that undergo peptide cleavage: digestive enzymes, fibrinogen (insoluble precursor of fibrin)

ADDITION OF HYDROCARBON AND FATTY ACID GROUPS

Hydrophobic isoprene & palmitoyl groups can be added to cysteine residues & myristoyl groups to amino termini --> make proteins more hydrophobic
10-20 carbon atoms – proteins can be membrane-associated

– covalent/reversible addition