Protein Folding Review

Question 1

interactions that govern protein folding stability

Answer 1

non-covalent

hydrophobic

Question 2

non-covalent interactions

Answer 2

Van der Waals interactions (short range repulsion)

hydrogen bonds

electrostatic forces (e.g. ion pairs and salt bridges)

Question 3

hydrophobic interactions

Answer 3

nonpolar groups do not interact favorably with water

their favorable interactions are primarily the results of their exclusion from water

the hydrophobic interaction is a major factor in the folding and stability

Question 4

determinants of folding

Answer 4

secondary structure (for an efficient packing)

hierarchical folding

hydrophobic effect

context dependent

Question 5

alpha helix is stabilized by intrachain hydrogen bonds between the _____ and ______ groups

Answer 5

NH

C=O

Question 6

hydrogen bonds in alpha helix form _____ amino acid residues ahead in the sequence

Answer 6

4

Question 7

alpha helices can be right (clockwise) and left handed, alpha helices found in proteins are _____ - handed because they are energetically more favorable

Answer 7

right

Question 8

beta sheets are stabilized by hydrogen bonding between _______ strands

Answer 8

polypeptide

Question 9

a beta sheet is formed by linking

Answer 9

2 or more beta strands via hydrogen bonds

Question 10

beta sheets can run in

Answer 10

parallel or antiparallel direction

Question 11

reversal directions in polypeptide chain provides

Answer 11

compact and globular shapes for polypeptide chain; they’re called reverse turn, beta turn, and hairpin turn

Question 12

in many reverse turns, C=O and N-H groups form

Answer 12

hydrogen bonds for stability

Question 13

loops do not have regular periodic structure, they are often ______ ; positioned ______ ; and participate in ______ and ______

Answer 13

well defined and rigid

on the surface of the protein

protein-protein interactions and interactions with other molecules

Question 14

heptad repeat

Answer 14

a type of random repeat sequence in which a group of 7 amino acids occurs many times in a protein sequence

often found in superhelix

Question 15

folding funnel steps

Answer 15

1. rapid formation of secondary structures
2. formation of domains through cooperative aggregation (concept of folding nuclei)
3. formation of assembled domains (concept of molten globule)
4. adjustment of conformation
5. more rigid structure

Question 16

molten globule state charactersitics

Answer 16

1. the presence of a native-like content of secondary structure
2. the absence of a specific tertiary structure produced by the tight packing of amino acid side chains
3. compactness in the overall shape of the protein molecule, with a radius 10-30 percent larger than that of the native state
4. the presence of a loosely packed hydrophobic core that increases the hydrophobic surface area accessible to solvent
5. it is not specific and occurs in early stage of protein folding

Question 17

tertiary structure

Answer 17

spatial arrangement of amino acid residues that are far apart in the sequence and to the pattern of disulfide (S-S) bonds

Question 18

protein disulfide isomerase (PDI)

Answer 18

rearranges the polypeptide’s non-native S-S bonds

fixes incorrect disulfide bonds

Question 19

protein folding is a highly ______ process

Answer 19

cooperative

Question 20

proteins can be denatured by several treatments to disrupt

Answer 20

the tertiary structure

Question 21

protein folding and unfolding in a ______ process

Answer 21

all or none

Question 22

molten globule stage is ______ and ______

Answer 22

intermediate

very short

Question 23

partially loss of folding destabilizes the

Answer 23

remainder of the structure

Question 24

quaternary structure

Answer 24

spatial arrangement of subunitS and nature of their interaction

Question 25

PPI (peptidyl prolyl cis-trans isomerase)

Answer 25

assists with cis-trans transition

Question 26

mitochondria contain their own _____ and _____ molecules that are distinct from those that function in the cytosol

Answer 26

Hsp60 Hsp70

Question 27

functions of molecular chaperons Hsp70/40

Answer 27

ATP-driven reverses misfolds; assists with newly synthesized proteins; unfold/refold of trafficked proteins

Question 28

chaperonins are a subtype type

Answer 28

chapernons

Question 29

molecular chaperon functions

Answer 29

1. essential proteins that bind to unfolded and partially folded polypeptide chains 2. they prevent the improper association of exposed hydrophobic segment 3. non-native folding, polypeptide aggregation, and precipitation will not occur 4. they allow misfolded proteins to refold into their native conformation

Question 30

native protein --> soluble --> _______ tries to refold, if not it ubiquinates and _____ assists with proteasoe

Answer 30

Hsp40 Hsp70

Question 31

native protein --> insoluble --> ______ and ______ ubiquinate and send to proteasome

Answer 31

Hsp40 Hsp70

Question 32

ubiquitinated proteins are processed to ______ ; which are further processed to yield ______ ; these can can used for

Answer 32

peptide fragments free amino acids biosynthetic rxns

Question 33

what structures or processes are involved in cellular quality control system

Answer 33

proteasomes autophagy ERAD (ER-Associated Degradation)

Question 34

how does protein-folding cause diseases? improper degradation

Answer 34

overactive cellular degradation systems (ERAD, autophagy) can contribute to the accumulation of mutant, misfolded, incomplete degraded proteins this improper degradation of proteins can contribute to the development of more severe diseases e.g. cystic fibrosis

Question 35

how does protein-folding cause diseases? improper localization

Answer 35

for proper trafficking to target organelles, proteins must fold correctly incorrectly folded proteins lead to improper subcellular localization (resulting in loss-of-function: protein isn't transported correctly to target organ so target organ cannot function properly or gain-of-function: protein isn't able to be transported out of original organ and causes dysfunction in organ where it was synthesized) e.g. AAT

Question 36

how does protein-folding cause diseases? dominant negative mutation

Answer 36

a mutant protein antagonizes the function of the wild-type protein leading to: loss of protein activity; and mutant protein presence interferes with function of the WT protein at cellular and structural levels e.g. p53

Question 37

how does protein-folding cause diseases? gain-of-toxic function

Answer 37

protein conformational changes can cause dominant phenotypes e.g. ApoE in Alzheimer's disease; Src kinases in cancer

Question 38

how does protein-folding cause diseases? amyloid accumulation

Answer 38

e.g. cataracts and alzhiemer's disease

Question 39

amyloid fibers

Answer 39

insoluble protein aggregates

Question 40

amyloidogenic proteins have ______ sequence

Answer 40

VQIVY

Question 41

lower order oligomers cause

Answer 41

toxic effect

Question 42

amyloid deposits could be a

Answer 42

protective mechanisms

Question 43

several amyloidogenic proteins from pore-like structures that

Answer 43

disrupts the cell membrane integrity

Question 44

misfolded forms of the protein are frequently observed in

Answer 44

the elderly as part of the natural aging process individuals with mutations in the protein early in life

Question 45

how do amyloid fibers progress to amyloid plaques

Answer 45

seeding (nucleation) --> fibril formation --> deposit

Question 46

keystones for environmental stress

Answer 46

to detect to respond to adopt

Question 47

intrinsic induction of stress defense programs and resulting adaptation can

Answer 47

increase life expectancy

Question 48

proteostasis

Answer 48

maintenance of protein homeostasis

Question 49

cellular and organismal functionality requires

Answer 49

protein production folding degradation

Question 50

complex pathways to ensure proteostasis in different compartments include

Answer 50

cytosol (Heat Shock Response) ER (UPRer) Mitochondria (UPRmt)

Question 51

cellular proteins are folded

Answer 51

by chaperons

Question 52

membrane and secreted proteins fold and mature where

Answer 52

in the ER

Question 53

what is the last line of defense in regards to maintaining proteostasis

Answer 53

apoptotic pathway

Question 54

heat shock response (HSR) manages denatured proteins in

Answer 54

the cytosol

Question 55

unfolded protein response ER (UPRer)

Answer 55

unfolded or misfolded proteins accumulate in ER causing ER stress ER stress initiates a single pathway called unfolded protein response (UPR) this pathway is intended to save the cell

Question 56

functions of UPRer

Answer 56

increase protein chaperones increase rate of ERAD decrease protein production last resort is apoptosis

Question 57

steps of autophagy

Answer 57

isolation membrane formation identification and collection of cellular components for degradation completion of autophagosome fusion of autophagosomoe with lysosome formation of autolysosome and degradation of contents

Question 58

steps of ERAD

Answer 58

translocation into ER degradation of misfolded proteins through translocation out of ER and into proteasome

Question 59

which UPR pathway is most recently discovered

Answer 59

UPRmt

Question 60

mitochondrial proteome is composed of how many proteins

Answer 60

1500

Question 61

mitochondria proteins are encoded by

Answer 61

nuclear and mitochondrial genome

Question 62

13 essential proteins of ______ are encoded by mtDNA

Answer 62

ETC

Question 63

what are the 2 major mitochondrial chaperon systems

Answer 63

mtHSP70 multimeric HSP60-HSP10 machinery in the matrix

Question 64

UPRmt protein quality control (PQC) proteases:

Answer 64

are specific for each mitochondrial compartment recognize and degrade the proteins that don't fold and that aren't properly assembled

Question 65

if the UPRmt senses the overload of the QC (quality control) system, it

Answer 65

activates the transcription of nuclear encoded protective genes by retrograde signaling re-establishes the mitochondrial homeostasis