SPP intramembrane aspartyl protease

memb-bound proteins or proteins destined for secretion are synth'd by ribosomes assoc w ER memb, contain signal peptide at N-Terminus, which binds with SRP (signal recocnition particle), which allows it to bind translocon in ER membrane

SPP cleaves SRP

pre-proteins vs pro-proteins

pre-proteins still have signal peptide at N-terminus

in pro-proteins, signal peptide has been cleaved by SPP

N-linked glycosylation

important in some EU protein folding

oligosaccharides (high-mannose oligos or complex oligos) are added to protein

further phosphorylation in Golgi of 1+ mannose residues

CDGs (congenital disorders of glycosylation)

lack ability to phosphorylate mannose residues-->

mutations in glycosylide oligosaccharide structures

multisystemic disorders w neurologic involvement

tx: enzyme replacement therapy

acetylation and methylation of aa

Lysine residues in histones

regulates gene transcription

acetyl=ON

methyl=OFF

aas often targeted for phosphorylation regulation

serine

threonine

tyrosine

Tyrosine sulfation

regulates protein structure

universal sulfate donor=PAPS

sulfation is NOT reversible

proteolytic processing for activity

proteins are activated after translation by modification

can be extracellular or intracellular

proinsulin

synthesized in ER of pancreatic Islet cells

proinsulin processing

moved from ER to Golgi, packaged into secretory vesicles, then processed by proteases-->mature insulin

N- and C-peptidases and proteolytic processing

modify procollagen extracellularly --> tropocollagen-->assemble into collagen fibrils

proteasome

protein complex with active sites for protein degradation inside

loc in cytosol and nucleus

Ubiquitin

a small protein tag that marks proteins for degradation

1. ubiquitin-activating enzyme binds ubiquitin to enz via ATP bond

2. uniquitin-conjugating enz transfer ubiq to substrate protein

3. ubiquitin-protein ligases-->covalent attachment of ubiquitin to internal Lys

4. degradation of protein, recycling of ubiquitin

defective ubiquitination-->

cancer, neurodegenerative diseases

SUMO-ylation

posttranslational modification

sim to ubiquitination, but NOT used to tag proteins for degradation

may provide docking/binding sites for protein-protein interactions