PROCESS
WHAT HAPPENS
WHERE
CLUE · DISEASE
Chaperones
heat shock proteins
Help nascent proteins fold; refold stress-damaged proteins
Cytosol, ER (BiP), mitochondria
Unfolded protein response when ER overloaded
Cleavage of signal peptides or pro-segments (zymogen → active)
ER, Golgi, secretory granules, extracellular
Proinsulin → insulin + C-peptide · trypsinogen → trypsin
Kinases add phosphate to Ser, Thr or Tyr; phosphatases remove it
Cytosol, nucleus
Main on/off switch of signaling
N-linked (Asn) begins in RER · O-linked (Ser/Thr) in Golgi
RER, Golgi
Congenital disorders of glycosylation
Proline and lysine hydroxylated in procollagen
RER; needs vitamin C
Scurvy (3.05)
Glutamate → γ-carboxyglutamate on clotting factors
ER of hepatocytes; needs vitamin K
Factors II, VII, IX, X, protein C, S · warfarin blocks
Chains of ubiquitin tag proteins for proteasomal destruction
Cytosol, nucleus
Bortezomib blocks proteasome (myeloma)
Signal recognition particle
Binds the N-terminal signal sequence and docks the ribosome on the RER
Cytosol → RER
Absent SRP → protein stays cytosolic
GlcNAc phosphotransferase marks lysosomal enzymes in the cis-Golgi → M6P receptors deliver them
Golgi → lysosome
I-cell disease: coarse face, gingival hyperplasia, clouded corneas, restricted joints, death by ~8 y; ↑ plasma lysosomal enzymes
COPII: ER → Golgi (anterograde) · COPI: Golgi → ER (retrograde) · clathrin: Golgi → lysosome, membrane → endosome
—
LDL receptor-mediated endocytosis uses clathrin
Nuclear & peroxisomal signals
Nuclear localization signal (basic residues) · peroxisomal targeting sequence (C-terminal SKL)
Imported after translation on free ribosomes
Zellweger: defective peroxisome import (3.02)