4 Protein Targeting

cytosolic ribosomes, RER-associated polyribosomes; classification based on site of protein synthesis

chemically identical

• 1) cytosol
• 2) mitochondria
• 3) nucleus
• 4) peroxisomes

1) stay in the ER 2) be secreted (secretory vesicles) 3) Golgi 4) lysosome 4) plasma membrane

the first two dozen amino acids of a protein that specify which part of the cell the protein is going to; the signal is located on a protein's N-terminus, or 5' end, the end that's synthesized first

5-7 basic amino acids (small)

20-25 hydrophobic amino acids at the N-terminus; happens DURING translation, ribosome mRNA complex subsequently moves to ER & docks

SKL (tri-peptide serene lysine leucine); located on the C-terminus; a defect in SKL means the peroxisome won't have proteins to degrade 'toxins'

KDEL (tetra peptide sequence); used to retrieves proteins that try to escape from ER

mannose-6-phosphate; mannose 6-phosphate kinase adds phosphate to 6th position on a mannose sugar in the protein

proteins that complex with nascent polypeptides & if they sense they're folded properly, direct them to their destination

the proteosome

organelles that break down oxidative products, detoxify cells, and contain enzymes that destroy free radicals

• 1) Zellweger Syndrome
• 2) NALD (neonatal adrenoleukodystrophy)

the OUTSIDE of the cell

packages proteins inside the cell before they are sent to their destination; cis golgi = near nucleus; trans golgo = farther from nucleus

1) goes from the ER to the Golgi; in the ER proteins have been translated, sorted, and have had initial sugar additions

2) cis golgi network: phosphorylation & sorting

3) cis cisterna: trim sugars, more sorting

4) medial cistern: trim sugars, add sugars, & SORT

5) trans cistern: add sugars, sorting

6) trans golgi network: process proteins, sort

• send vesicles to one of 3 places:
• 1) lysosome
• 2) plasma membrane
• 3) secretory vesicles

• 1) lysosome
• 2) plasma membrane
• 3) secretory vesicles

organelles with acid hydrolase enzymes that break down waste materials and cellular debris; enzymes work best at low pH achieved by H+ ATPase pump in lysosome membrane (ph = 5)

• 1) Hunter's
• 2) Fabry's
• 3) Goucher's

proteins are not properly targeted for lysosome in the Golgi; M6P signal is missing; end up being secreted; build up of substances in lysosomes because there's no enzyme to degrade them

another protein targeting disease: cytoplasmic proteins accumulate in nucleus because of mutation that creates NLS signal

• I-Cell
• Tay-Sachs
• Fabry
• Gaucher
• Pompe
• Gangliosidoses
• Mucopolysaccharidoses
•   -Hurler's
•   -Pseudo-Hurler's
•   -Hunter
•   -Sanfilippo
•   -Morquio
• Sulfatase deficiencies
• Beta-Galactosidase (enzyme) deficiencies
• *Niemann-Pick

lipid storage disorder caused by the accumulation of gangliosides, a TYPE of sphingolipid