Kandpal - Protein Targeting and Vesicular Trafficking Flashcards
what do the ribosomes do that are free in the cytosol
synthesize cytoplasmic, nuclear, and mitochondrial proteins
what do the bound/ER ribosomes synthesize
secreted proteins, plasma membrane proteins, ER proteins, golgi proteins and lysosomal proteins
what is a nuclear localization sequence (NLS) on a protein
either a signal sequence on the N-terminal or a signal patch in the center of the protein that are hydrophobic
what is the signal hypothesis
translation in the presence of ribosomes = larger proteins and in the presence of microsomes = smaller proteins
what are 3 types of protein traffic
gated transport, transmembrane transport, and vesicular transport
where does gated-transport occur, how does protein enter and does it require ATP
cytosol -> nucleus, through pore complexes (nucleoporins), yes
how do import receptors work in gated transport
protein NLS binds to nucleoporin -> cargo is delivered to nucleus -> Ran-GTP binds to receptors -> leaves nucleus -> Ran-GDP dissociates from receptor
how do export receptors work in gated transport
Ran-GTP binds to receptors -> protein + nuclear export signal leave nucleus -> Ran-GDP dissociates and cargo is delivered to cytosol
what regulates GTP and GDP in gated transport
GTPase activating protein (GAP) in cytosol and guanine exchange factor (GEF) in nucleus
in the transmembrane transport from cytosol to mitochondria, what is the signal peptide and where is it located
a helical structure with + charged clusters on one side and - charged regions on the other
at the N-terminus
what 2 things are located on the outer membrane for transmembrane transport
TOM (translocation channel/receptor) and SAM complex
what 2 things are located on the inner membrane for transmembrane transport
TIM 23 complex (Hsp70 import ATPase) and OXA complex
where is the signal located for cytosol-> peroxisome transport
3 amino acid sequence at the C-terminus
what happens in peroxisome transport disorder -> Zellweger Syndrome
mutations in transport protein Pex2 - leave empty peroxisomes
which type of transmembrane transport has translation and translocation at the same time
cytosol -> endoplasmic reticulum
what recognizes the signal sequence in the cytosol for ER transport
signal recognition particle (SRP) - complex 300 nucleotides, 7SL RNA and 6 proteins
after SRP recognizes signal sequence in cytosol for ER transport - what does the protein bind to
binds on the nascent protein, large ribosomal unit and SRP receptor (Methionine residues on p54 bind to signal sequence) and hydrolyzes GTP
there are 4 topological classes or proteins (cytosol -> ER space/lumen) what are the based on
classified by orientation, transmembrane domains, and signal sequences
what is the cleavable signal on Type 1 topological protein
cleavable signal is “COO-“ on cytosol and the hydrophobic residues stop transport and gets embedded into membane
what is the cleavable signal on Type 2 topological protein
no cleavable signal - but NH3+ is in cytosol
what is the cleavable signal on Type 3 topological protein
no cleavable signal but has hydrophobic regions that stop transport and get embedded into membrane
what is the cleavable signal on Type 4 topological protein
multiple
secretory proteins have a coat in vesicular transport, what are the 3 types of coats
clathrin, COPI, and COPII
what are the steps for vesicle formation and fusion in vesicular transport
coat-recruitment by GTPase control, Rab proteins regulate flow of vesicle to correct membrane and SNARE proteins mediate fusion
what are the 2 paths for secretory proteins
constitutive pathway or regulated pathway
what happen in the constitutive pathway (unregulated) for secretory proteins
after golgi sorts into vesicles -> has unregulated fusion into extracellular space (occurs all the time)
what regulates the regulated pathway in secretory proteins
hormone or neurotransmitter (only occurs when signal occurs)
what do lysosomes store
hydrolytic enzymes - glycosidases, proteases, phosphatases, and sulfatases
what “tag” do lysosomal hydrolases carry
unique “mannose-6P” tag on N-linked oligosaccharide that is recognized by receptor on lysosome
what is I-cell disease
lysosomal storage disease
what happens with a deficiency of mannose-6P attaching enzyme
no transport of lysosomal enzymes to lysosomes -> accumulation in circulation
what are 3 endocytic pathways
phagocytosis, pinocytosis, and receptor-mediated endocytosis
what is autosomal dominant hypercholesterolema caused by
mutations in LDL (low density lipoprotein) receptor - which normally removes LDL from circulation
what are 2 protein modifications that occurs after translation
glycosylation at OH groups of serine and theronine residues (O-linked) or amide group of asparagine (N-linked) and disulfide bonds are added for folding
what does a1-antitrypsin do (secreted from hepatocytes and macrophages)
inhibits trypsin and blood pretease elastase
what does a deficiency in a1-antitrypsin cause
hereditary emphysema - and an absence leads to elastase degrading lung tissue
