Protein Trafficking & Virion Assembly

proteins that are synthesized on free ribosomes in cytosol

cystolic, peripheral, lipid-anchored, nuclear, mitochondrial

proteins that are synthesized on rough ER

integral, secreted, lumenal (lipid-anchored)

prenylation

post translation modification in which cells attach hydrophobic lipid groups (farnesyl or geranylgeranyl) to specific target proteins by recognizing specific target sequence at end of protein (CaaX box) on C terminus

myristoylation

permanent, co-translational protein modification, myristic acid covalently attached to N terminal glycine residue, irreversible

glycophosphatidylinositol (GPI)

glycolipid structure used by cells as specialized anchor to attach proteins to outer leaflet of cell membrane, tethered by lipid tails to allow greater mobility

nuclear localization signal (NLS)

short stretch of amino acid sequence that direct newly synthesized proteins from cytoplasm into nucleus of euk. cell, makde by free ribosomes

importin

transport receptor proteins responsible for recognizing and carrying macromolecules (destined for nucleus) thru nuclear pore complex (NPC) from cytoplasm into nucleoplasm

nuclear pore

protein channel in double membrane nuclear envelope that is gateway for macromolecular traffic of nucleus

1. tag with NLS

2. importin binds to cargo in cytoplasm and brings to nuclear pore

3. importin-cargo complex diffuses thru nuclear pore

4. protein dissociates from importin once in nucleus

post-translational import into nucleus

nuclear export signal

tags proteins for export from nucleus thru nuclear pore complex

exportin

transport receptor protein responsible for recognizing and carrying macromolecules out of nucleus

1. exportin binds to NES tagged protein

2. nuclear pore transports exportin-protein complex

3. protein dissociates from exportin in cytoplasm

post-translational export from nucleus

nucleoporins

proteins that make up nuclear pore complex, gateways embedded into double membrane nuclear envelope, ~30 types

diffuse freely through pore

<40 kDa proteins

require importin/exportin

>40 kDa proteins

chaperone/unfolding activity

actively refold misfolded proteins, feed proteins through narrow membrane channels by unfolding them

mitochondrial targeting sequence

amino acid sequence located at N-terminus of newly synthesized nuclear-encoded protein, directs its transport into mitochondria

co-translational import

proteins destined for ER, golgi, lysosomes, membrane, secretion are synthesized and simultaneously threaded across ER while translation still occurring on ribosome

topogenic sequences

dictate how protein is intgrated into or translocated across cellular membranes (ER) during co-translational importc(eg. signal, stop-transfer, start-transfer)

triskelions

three-armed structural protein complex, building block of clathrin coats

clathrin

structural protein complex that plays role in vesicle formation and intracellular trafficking, drives receptor-mediated endocytosis and transport of molecules from Golgi to endosomes

adaptor proteins

connect cell-surface receptors, cargo molecules, and structural coats during intracellular transport and cell signaling

receptor-mediated endocytosis

energy-dependent cellular process by which cells selectively internalize specific extracellualar molecules (eg hormones, growth factors) by trapping them in membrane-bound vesicles, pull in specific molecules by recognizing target ligands

endosome

membrane-bound compartment that is central sorting station for endocytic pathway

COPI

protein complex that coats vesicle membranes to mediate retrograde transport - ships proteins and lipids backward from golgi to ER

COPII

protein complex that voats vesicles to carry newly made proteins forward from ER to golgi

1. formation of disulfide bonds

2. proper folding

3. specific proteolytic cleavages

4. assembly into oligomeric proteins

5. addition and processing or carbohydrates (glycosylation)

5 post-translational modifications that occur in rough ER

oligosaccharides

carbohydrate molecules formed when a small number of monosaccharides are linked togther by glycosidic bonds

O-linked oligosaccharides

type of protein glycosylation where sugar molecule is added to oxygen atom in hydroxyl group on serine or threonine, shorter

N-linked oligosaccharides

sugars linked to nitrogen on asparagine, long and highly branched

glycosylation

enzymatic attachment of carbohydrate sugar chains to amino acid residues of a target protein/lipid molecule