Functions and dysfunctions of protein processing Flashcards Preview

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Flashcards in Functions and dysfunctions of protein processing Deck (66):
1

Describe a silent mutation

A point mutation occurs, but it does not change the amino acid

2

Describe a missense mutation

A point mutation occurs, leading to a different amino acid

3

Describe a nonsense mutation

A point mutation occurs which leads to a stop codon. The protein synthesis stops there

4

Describe a frame shift mutation

Nucleotides are added or deleted, making all amino acids downstream incorrect

5

Describe sickle cell anemia

A missense mutation leads to a substitution of Val (hydrophobic) to Glu (negative). The protein (HbA) aggregates and RBCs are deformed

6

Describe Duchenne muscular distrophy

A large frame shift mutation occurs, leading to non-functional dystrophin. Leads to muscle wasting (wheelchair 12yrs and respiratory failure around 14yrs)

7

Describe the structure of mRNA

7-methylguanosine cap at the 5' end and polyA at 3' end. The coding region is located between two untranslated regions.

8

Describe tRNA

Cloverleaf shape;
anticodon loop is complementary to mRNA;
3'CCA terminal region where aa is attached

9

describe aminoacyl tRNA synthetase

attached appropriate tRNA to it's aa

10

why is aminoacyl tRNA synthetase considered the "second genetic code"?

It binds the correct aa to it's correlated tRNA. If this makes an error, then the wrong protein will be translated. It is the same as if it was transcribed incorrectly from the DNA

11

Describe ribosomes

translation center; 2 subunits; different in structure in eu vs prokaryotes
3 sites of action

12

why is the different structure in eukaryotic ribosomes and prokaryotic chromosomes significant?

certain antibiotics and toxins can target one organism's while not effecting the other

13

What are the 3 sites on the ribosome? what do they do?

Acceptor site-where mRNA sites to interact with tRNA
Peptidyl site-where tRNA attaches
Empty/Exit site-where empty tRNA sits before exiting ribosome

14

what are the 3 stages of translation?

initiation, elongation, termination

15

describe initiation phase of translation

formation of mRNA, small subunit and initiator tRNA make a complex

16

Describe the elongation phase of translation

activated by AA attached to Met by forming peptide bond

17

Describe termination phase of translation

peptide chain is release from ribosome

18

What is the start codon in mRNA? Why is that significant?

AUG;
initiator rRNA is scanning for it to begin building polypeptide

19

What is eIF4E and eIF4G?

What are Eukaryotic initiation factors (eIFs)?
eIF4E (rate limiting step of translation because it's got to meet ribosome)

20

What are Eukaryotic initiation factors (eIFs)?

proteins involved in the initiation phase of eukaryotic translation. These proteins help stabilize the formation of the functional ribosome around the start codon and also provide regulatory mechanisms in translation initiation.

21

What is eIF2?

eIF2 mediates the binding of tRNAiMet to the ribosome in a GTP-dependent manner.
It is hydrolized (released to form GDP) when tRNA finds the AUG codon

22

When does the large subunit bind in translation?

once AUG is found by tRNA and eIF2 is released from tRNA-Met molecule (making room for large SU).

23

When does the aminoacyl tRNA bind to ribosome?

After large SU attaches to small SU

24

When is the first peptide bond formed in the ribosome?

once the aminoacyl tRNA binds to the ribosome it then binds the aa with the initiator tRNA's Met

25

What is the name for initiator tRNA when Met is attached? is it different in prokaryotes?

methioninyl tRNA;
N-formylmethiononinyl tRNA is prokaryotes

26

What are EF-1 and EF-2?

elongation factors. The first facilitates the loading of aatRNA to A-site, the second facilitates the shifting of tRNA down to the next site to vacate the A-site for the next aatRNA (prokaryotes EF-Tu adn EFG)

27

What is used to power enlongation?

GTP is bound to elongation factors and the hydrolyzation of it releases the factors

28

Describe peptidyl transferase and it's function

it is located on the ribosome and it catalyzes the peptide bonding. It is regulated by rRNA.
Energy for this rxn comes from high energy bond between aa and tRNA

29

Describe the steps of termination

-Stop codons UAA,UAG or UGA terminate translation
-release factor (RF) binds to A-site;
-peptide released when RF moves to P-site
-COOH added to peptide
-GTP hydrolysis dissociates ribosome complex

30

how many GTP used in each step of translation?

one to initiate
two per amino acid to elongate
one to terminate

31

How does diptheria toxin work?

inactivates EF2-GTP to inhibit elongation

32

How does shiga toxin, streptomycin, clindamycin, tetracyclines work?

binds to ribosome subunit to disrupt translation

33

What signal needs to be added to a protein to send it to the cytoplasm?

no signal;

34

What signal needs to be added to a protein to send it to the mitochondria?

N terminal hydrophobic alpha helix

35

What does the N terminal hydrophobic alpha helix do?

it helps traffic proteins to the mitochondria;
it also helps proteins interact with chaperone proteins (heat shock: protect linear structure of proteins)
It also is recognized by transporters on mitochondrial membranes (TIM & TOM)

36

Describe mitochondrial protein import

Protein has signal sequence on it
-signal recognized by TOM complex
-protein sent linearly through TOM and TIM
-peptidase is in matrix to cleave signal i think

37

Describe nuclear import of proteins

nuclear pores allow small proteins through
Large proteins >40kDa require nuclear location signal (4 continuous basic residues i.e. Lys and Arg)

38

What are cytoplasmic protein pathway destinations?

cytoplasm, mitochondria, nucleus, peroxisomes

39

What is the nuclear signal sequence for proteins?

KKKRK

40

What is the peroxisome signal sequence for proteins?

SKL
Ser, lys, leu

41

What are the destinations of the secretory pathway of protein sorting?

ER lumen, lysosomes, secretion, and membranes

42

What is the signal sequence for sending proteins to the ER lumen?

C-terminal KDEL retention signal

43

What is the signal sequence for sending proteins to lysosomes?

Mannose 6-phosphate signal group
I-cell disease

44

What is the signal sequence for secretion of proteins?

Tryptophan-rich domain signal sequence, Absence of retention motifs

45

What is the signal sequence for sending proteins to the membrane?

N-terminal apolar region (stop transfer sequence

46

What is KDEL?

ER lumen protein sequence;
K-lysine, D-aspartic acid, E-glutamic acid, L-leucine

47

Describe the secretory pathway

protein has to go to ER to finish translation, then it is modified in the ER or Golgi

48

How does protein get tranlated into the ER?

-ER signal on N cap of protein on ribosome
-15-60aa on N terminus
-1 or two basic aa (Lys or Arg) near N terminus
-extreme hydrophobic sequence on C terminus of these basic residues
-SRP binds ER signal
-SRP receptor binds it to ER
-peptidase cleaves signal to restart translation into ER through protein translocator

49

describe chaperones and chaperonins

Chaperones aid in folding the protein correctly
Chaperonins are large, barrel structures that fold proteins inside with ATP energy

50

Describe HSP60

heat shock protein 60 is a chaperonin inside the mitochondria which aids in preventing misfolding of protein in stress and other times

51

describe HSP70

heat shock protein 70. The Hsp70s are an important part of the cell's machinery for protein folding, and help to protect cells from stress

52

describe proteolytic cleavage

converts active enzymes by unmasking the active site.
it cleaves part of the zymogen and exposes the active site

53

name examples of proteolytic cleavage

trypsinogen (all in trypsin family
proinsulin to insulin

54

What are four post-translational modifications

glycosylation,
phosphorylation,
disulfide bond formation,
and acetylation

55

Describe glycosylation

extracellular proteins,
covalently linked to sugar in ER lumen,
o-glycosidic or n-glycosidic linkage

56

how are o-links formed in glycosylation?

hydroxyl groups of Ser or Thr residues

57

how are n-links formed in glycosylation?

Asp;
precursor sugar transferred from phospho Dolichol

58

Describe phosphorylation of proteins

Ester bond is formed between phosphate and OH of aa
Serine/threonine/tyrosine kinases

59

Describe disulfide bond formation

inter and intra-molecular disulfide bonds stabilize proteins
form between thiol (SH) group of cysteines
formed IN ER by protein disulfide isomerases

60

Describe acetylation

acetyl CoA is donor
lysine residues acetylated
Histones are Acetylated or deacetylated on N terminal
histone modifications are heritable

61

What role does vitamin C play in

Ascorbic acid is important to form lysyl hydroxylases
These enzymes are essential to collagen modification/assembly
Think lysine deamination and proline hydroxylation

62

What could defects in Lysyl hydroxylases result in?

skin, bone, and joint disorders:
Ehlers, Danlos, Nevo, Bruck, Epidermolysis

63

Describe Alzheimer's disease

-Amyloid beta peptide is misfolded and forms plaques in brain (extracellular)
-hyperphosphorylation of Tau (neurofibrillary tangles; intracellular)
These are familial forms. Sporadic form is just from brain aging.

64

Describe Parkinson's disease

aggregation of alpha-synuclein protein forms insoluble fibrils which deposit as Lewy bodies in dopaminergic neurons in substantia nigra
-results in death to neuron
-symptoms because of no dopamine
-mutations to AS cause familial form, brain aging is sporadic form

65

huntington disease

huntington gene mutation results in expansion fo CAG triptlet repeats
results in polyglutamine repeats in HTT protein
-misfolds and aggregates
-selective death of cells in basal ganglia causes symptoms

66

describe creutzfeldt-jakob disease

prions
infectious- causes other proteins to misfold
Transmissible spongiform encephalopathies (TSEs)