Functions/Dysfunctions of Protein Processing

Question 1

TOM

Answer 1

Translocation sequences are recognized by Transporters in the Outer Membrane (TOM

Question 2

TIM

Answer 2

translocation sequences are recognized by Transporters in the Inner Membrane (TIM)

Question 3

Translocation complexes allow

Answer 3

signal protein to be passed through the inner and outer mitochondrial membrane

Question 4

silent mutation

Answer 4

no change to the amino acid

Question 5

missense mutation

Answer 5

changes amino acid in the protein with either no effect in function or a VERY different function

Question 6

nonsense mutation

Answer 6

codon changes into a stop codon causing premature stop. Protein either degraded or truncated

Question 7

Frameshift Mutation

Answer 7

one or more nucleotides deleted or inserted into ORF. OOF mutation changes codon/amino acid (DMD)

Question 8

Sickle Cell Anemia

Answer 8

missense mutation of HBB

changes GAG to GTG-glutamate (hydrophilic) to valine (hydrophobic)

causes HbA to aggregate, make rod structures

deforms RBCs, sickle shape.

poor O2 capacity, clog capillaries and restrict blood supply

Question 9

DMD

Answer 9

frameshift mutation (OOF) deletions in the dystrophin gene

little to no expression of dystrophin

muscle wasting

if an IFM occurs, results in truncated dystrophin causing milder BMD

Question 10

Cytoplasmic Pathway

Answer 10

protein goes to cytosol, mitochondira, nucleus, perioxisomes

protein synthesis begins and ends on free ribosomes

Question 11

Secretory Pathway

Answer 11

protein goes to ER, lysosomes, plasma membranes, secretion

translation starts on free ribosomes, ends on ribsomes that are sent to the ER

Question 12

Proteins destined for ER lumen us the signal

Answer 12

C-terminal KDEL retention signal (lysine, aspartic acid, glutamic acid, leucine)

Question 13

proteins destined for the lysosomes use the signal

Answer 13

mannose 6 phoshate

. DEFECT is I cell disease

Question 14

proteins destined for secretion use the signal

Answer 14

tryptophan rich domain

Question 15

proteins destined for secretion in membranes use the signal

Answer 15

N terminal nonpolar (GAPVIL M/W/F)

stop transfer sequence

Question 16

Nuclear import occurs via

Answer 16

localization signals for larger proteins. signals consist of Lys Arg repeats (4) (KAKA)

Question 17

Overview of secretory pathway

Answer 17

each protein has an ER targeting signal peptide 15-60 AA at the N terminus

1-2 basic AA (KA) near N terminus or hydrophobic sequence on C terminus of the basic residues

Signal recognition particle wraps around ribosome-mRNA -peptide complex tying it to ER membrane and stopping translation

Enzymes will cleave the signal to release the protein which can then continue on its journey

Question 18

I cell disease

Answer 18

tagging of lysosomal proteins with manose 6 phosphate is defective

proteins not sent to lysosomes

high plasma levels of lysosomes

FTT, developmental delays, death.

Question 19

Chaperones

Answer 19

help large proteins fold into 3’ state

Question 20

Chaperonins

Answer 20

barrel shaped compartments that admit unfolded proteins and catalyze folding in ATP dependent manner.

Question 21

Proteolytic cleavage

Answer 21

converts inactive forms to active enzymes by unmasking active site

converts nascent precursor proteins to mature ones (proinsulin to insulin)

Question 22

O-glycocidic (glycocylation)

Answer 22

O-links are formed with OH groups of Ser, Thre

Question 23

N-glycosidic linkage (glycosylation)

Answer 23

N-links are formed always with Aspargine transferred from phospho Dolichol

Question 24

Phosphorylation forms

Answer 24

ester bond between P and OH of AA using Ser/Tyr kinase on Ser, Tyr, Thr, Asp, His

P removed via phsophatases

regualtes enzyme activity and function as well as cell growth, proliferation, oncogenes

Question 25

Disulfide Bond Formation

Answer 25

forms intra and inter moleceular bonds to stabilize proteins

thiol SH group between 2 cys

formed in ER lumen

uses protein disulfide isomerase

Question 26

Acetylation

Answer 26

proteins are acetylated on lysine residues

use acetyl CoA

acetylated and deacetylated on their N terminal critical for gene regulation

acetylation catalyzed by HAT, deacetylated but HDAC

pattern of histone modifications are heritable

Question 27

PTM of collagen

Answer 27

collagen is a trimer

lysines within are modiied to form 5-hydroxylysines

modifications important for assembly of collagen

Ascorbic acid essential for activity of lysl and porlyl hydroxylases

defects in lysyl hydroxylase casuses ED syndrome (overly flexible) and Epidermolysis Bullosa Simplex (blisters)

Question 28

ribosomes in eukaryotes these subunits

Answer 28

40S and 60S

compared to prokaryotes with 30S and 50S

important for drug targets

Question 29

Review LOs 1 and 2

Answer 29

know what ribosomes, mRNA, tRNAs and aminoacyl tRNAs, aminoacyl tRNA synthetases, and activation of amino acids

know initiation, elongation, termination in translation