Membranes III Flashcards
exam 1
the first ___-____ aa translated will determine if the protein continues to be translated in the cytoplasm or contains the _____ ____ that will cause the ribosome/nascent protein complex to relocate to the ER to finish translation of the protein
the first 20-25 aa will determine if the protein continues or contains the Signal Sequence
possibles fates of proteins that are translated completely on cytoplasmic ribosomes (4)
(1) cytoplasm
(2) nucleus
(3) mitochondria
(4) peroxisomes
possible fates of proteins that finish translation in the ER (5)
(1) plasma membrane
(2) ER
(3) golgi
(4) lysosomes
(5) secretion
mucopolysaccharidoses is an
LSD
why is I-Cell disease important?
it revealed the mannose-6-phosphate address label for lysosomal enzymes, opened up the whole field of LSDs, and taught us how lysosomes and several other organelles are made
In I Cell disease, the defect is in the ________________ enzyme that _________ the 6-position on specific ______ residues
the defect is in the phosphotransferase enzyme that phosphorylates the 6-position on specific mannose residues
targeting signal for all lysosomal enzymes
6-position on mannose residue
lysosomal enzymes are secreted from the cell, leaving lysosomes as an empty bag devoid of degradation enzymes
I-Cell
consequence of the I-Cell defect
lysosomes fill up with all the substrates they usually degrade and appear under the microscope as large, dark inclusion bodies
Protein targeting sequence 1
S-K-L is the tripeptide sequence that targets proteins to the peroxisome
Protein targeting sequence 2
short (typically 5-6) basic aa sequences are the NLS
Protein targeting sequence 3
mannose-6-phosphate targets proteins to the lysosome (its the only non-peptide address label)
Protein targeting sequence 4
a longish (about 75 aa) sequence near the N-terminal end of the protein directs proteins to mitochondria
Protein targeting sequence 5
K-D-E-L is the tetrapeptide sequence targeting proteins to the ER (it is actually an ER retention signal)
peroxisome targeting disease
Neonatal adrenoleukodystrophy (NADL) and Zellweger syndrome
nuclear targeting disease
Huntington’s
invagination
RME- receptor mediated endocytosis
clathirin is on the ____ side for RME
cytoplasm
clathirin coated vesicles are called
endosomes
homozygous condition on the dark side of RME leading to high LDL
familial hypercholesterolemia
Infleunza and rabies virus gets into the cell by
RME
Many viruses use RME to get inside the cell, then fuse with the _________
endosomes
true or false: clathirin help concentration of the ligands by sending a signal
true
true or false: all protein synthesis occur in the cytoplasm
true
SKL
presoxisomes
KDEL
ER “keep in the ER”
long, N-terminal aa sequence
mitochondria
short, basic aa sequence
nucleus
important signal for dilated mycocardiopathy
plasma membrane
recognize miss-folded proteins
chaperones
inducible by conditions that cause unfolding of newly synthesized proteins
Heat shock proteins
transmembrane protein in the ER membrane needs a
stop-transfer sequence
stacks of cisterne
golgi
cis golgi
close to the nucleus
trans golgi
close to the plasma membrane
phosphorylation of proteins destined to be _______ _______occurs at the ______ golgi
phosphorylation of proteins destined to be lysosomal enzymes occurs at the cis golgi
processing and sorting occurs at the ______ golgi
trans
lysosomes are full with ______ enzymes that work best at the ____ ph achieved by the _____ pump
lysosomes are full with degradative enzymes that work best at the low ph achieved by the H+ pump
low ph in an endosome allows for
a vesicle to be pinched off containing the receptor to be recycled
deficiency in iduronate 2-sulfatase
MPS dx–> hunter’s disease
caused by a defective phosphototransferase, such that lysosomal enzymes do not get properly tagged
I-Cell
where do the proteins destined for the lysosome acquire a phosphate group on the 6-positon mannose
Cis golgi body
if the first 20-25 amino acids on a proteins N-terminal are not hydrophobic, the completed protein’s default destination is the
cytoplasm
a protein will be transported to the ____ if it has a hydrophobic signal peptide
ER
4 fates of protein that finishes translation in cytoplasms
- Nulceus
- Mitochondria
- Peroxisomes
- Cytoplasm
- fates of protein that finished translation in membrane-bound ribosome
- E.R.
- Plasma membrane
- Secretory Vesicles
- Lysosomes
- Golgi
Nucelar localization signal (sequence)
Lys-Lys-Lys-Arg-Lys
Diseases of peroxisomal targeting (2)
- Zweller Syndrome
2. NALD
Golgi membrane between cis and trans
Medial region
3 fates of proteins that go through golgi
- Lysosome
- Plasma membrane
- Secretory vesicle
pH of lysosomes
5
Low lysosomal pH is achieved by
H+ pump
Lysosome deficiencies are due to a single _______
Lysosome deficiencies are due to a single enzyme deficiency
Targeting signal of nucleus
Short basic aa sequence
Pathology of problem with targeting signal of nucleus
Huntington
Targeting signal of peroxisome
SKL tripeptide
Targeting signal of mitochondria
70-80 aa sequence near N-terminus
Problem with targeting signal of mitochondria
mitochondriopathies
Targeting signal of lysosome
Mannose-6-phosphate
Problem with targeting signal of lysosome
I-cell disease
Targeting signal of ER
KDEL tetrapeptide
Problem with targeting signal of ER
Dilated cardiomyopathies
Sphingolipid metabolism defect; first LSD successfully treated with enzyme replacement therapy
Fabry
Sphingolipid metabolism defect; also successfully treated with enzyme replacement therapy
Gaucher
Sphingolipid and glycosaminoglycan (GAG) metabolism defect prevalent in Ashkenazi Jews
Tay-Sachs
Defect in one of the several enzymes needed to break down GAGs (aka mucopolysaccharides); several are now treated with enzyme replacement or enzyme enhancement therapies
Mucopolysaccharidoses (MPS)
Defect in the phosphoryltransferase that puts a phosphate group on the 6-position of specific mannose residues; no lysosomal enzymes get to lysosomes, thus all substrates constipate the lysosome; rare disease that revealed mechanisms for LSD pathogenesis and lysosomal/organellar biogenesis
I-Cell Disease
Key Point: While each individual LSD has an incidence of 1 in 100,000 or less, there are so many of them that the overall likelihood of an individual having an LSD is about 1 in _____
3000
