Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Biol 200 > Lecture 21 - Protein folding, misfolding and degradation > Flashcards

Lecture 21 - Protein folding, misfolding and degradation Flashcards

1
Q

Important component of tertiary structures and its definition

A

Domains. 100-150 a.a long regions, COMPACTLY FOLDED an that can be made of various motifs. Doesn’t depend on other parts of protein to fold itself

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Possible shapes of domains (2 ex,)

A

fibrous or globular

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Exemple of protein with fibrous and globular domain

A

HA2 protein in influenza virus hemagglutinin (interacts with HA1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Meaning of modular nature of protein domains

A

Can be found in diverse proteins or in multiple similar copies within a given protein. Domains can be shuffled because they fold independently of the rest of the protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is EGF and where does it come from

A

epidemical growth factor (1 domain). Comes from EGF precursor which is a protein with many EGF domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Domains can be found in multiple copies in same prots or in different prots. what is conserved and what is not

A

a.a sequence is not the same but 3D shape is the same

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

multimeric proteins is an aspect of _________ structure.

A

quaternary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

multimers covalent or non covalent bonds

A

non covalent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Supramolecular complexes is an aspect of _________ structure. Can have a MW of more than _______ and can also contain _______

A

quaternary. more than 1 MDa. nucleic acids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Supramolecular complex def

A

Molecular machines mad of multiple distinct proteins that have multiple subunits.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Supramolecular complex 2 exemples

A

transcription initiation complex, nuclear pore complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Main forces that hold tertiary quaternary structure vs main forces that hold secondary structure

A

tertiary quaternary -> H bonds, hydrophobic interactions and +/+ +/- interactions
secondary -> ONLY H bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Hemoglobin is a ____mer. What’s its structure ? Myoglobin is a ____mer. Leghemoglobin is a _____mer.

A

Hb tetramer. 2 alpha chains and 2 beta chains.

Myoglobin and leghemoglobin are monomers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Where hemoglobin, myoglobin and leghemoglobin are found

A

hemoglobin -> vertebrates, myoglobin -> unvertebrates

leghemoglobin -> plants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

differences and similarities between beta subunit of Hb, myoglobin and leghemoglobin and why the similarity

A

myoglobin and beta subunit of Hb -> 30% a.a similarity.
leghemoglobin and beta subunit of Hb -> much less than 30% a.a similarity
similarities -> same 3D structures (look alike) -> 3D structure related to its function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what 3D structure ressemblence between beta subunit of Hb, myoglobin and leghemoglobin shows

A

all come from an ancestral oxygen-binding heme-carrying protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

2 forms of a protein that can be obtained in vitro

A

Native and denatured conformations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What can lead to protein denaturation (2 exemples)

A

Urea, heat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What happens when denaturation conditions are removed/reversed ?

A

Protein folds back into native form (right conformation) or could possibly misfold

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Main characteristic of misfolded proteins and what than can lead to

A

Hydrophobic residues on the surface (oil drop model not respected) –> Can lead to aggregation of misfolded protein by interactions between the hydrophobic patches on their surfaces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How refolding and nascent protein folding is thought to happen and how is misfolding related to that

A

Through a folding pathway with multiple steps. Incorrect folding can happen in one of these steps.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are chaperones

A

Proteins that help protein fold along the right pathway.

Will put back into an on-pathway folding the proteins that have an off-pathway folding

23
Q

What is the pathway that proteins that can’t refold go through ?

A

Protease pathway (gives the ‘‘irreversible accidents’’ category)

24
Q

How chaperones recognize misfolded proteins

A

Recognize exposed hydrophobic patches

25
Q

Chaperones regulation (what can lead to them being in higher/lower number)

A

Upregulated under conditions that lead to misfolded proteins accumulation, such as heat shocks.

26
Q

What are HSPs and important side note

A

Heat-shock proteins -> synonym for chaperones. Chaperones aren’t only upregulated by heat

27
Q

5 things chaperones can do

A

1) Fold newly made proteins
2) Refold misfolded or unfolded proteins
3) Disassemble potentially toxic protein aggregates (that form due to misfolding)
4) Assemble/dismantle large multiprotein complexes
5) Mediate transformations between inactive and active forms of some proteins

28
Q

2 major classes of chaperones and their difference

A

1) Molecular chaperones (operate as single molecules)

2) Chaperonins (multisubunit refolding chamber)

29
Q

How chaperones work in general

A

ATP-dependent cycle of binding and release of misfolded client. Covers hydrophobic patches while torsions facilitate correct refolding

30
Q

Major MOLECULAR chaperone (+ most studied) and what it does

A

Hsp70. Helps newly-synthesized proteins follow the correct folding pathway

31
Q

2 important subunits (it has 3 subunits) on Hsp70

A

Substrate-binding site and nucleotide-binding site (for ATP)

32
Q

First step of Hsp70 mode of action + something particular about this step

A

Rapid protein binding (reversible, probably because low enthalpy/entropy step)

33
Q

Second step of Hsp70 mode of action

A

ATP hydrolysis (ADP stays and Pi leaves) and conformational change –> closed substrate-binding site (substrate is locked)

34
Q

Third step of Hsp70 mode of action

A

ADP release and ATP binding + end of correct folding

35
Q

Fourth (last) step of Hsp70 mode of action

A

Protein release (after proper folding finished)

36
Q

T/F : Hsp70 acts on a newly made protein when it’s out of the ribosome

A

F : Can also start helping it fold as elongation of the peptide is happening.

37
Q

Why chaperones bind to hydrophobic patches specifically

A

to prevent protein aggregation

38
Q

Other name for chaperonins and what they do

A

Hsp60’s : Form a chamber made of inward-facing protein-binding subunits that undergo ATP binding and hydrolysis and conformation change

39
Q

Structure of chaperonins

A

2 barrels and a cap.

40
Q

What is ubiquitin

A

76 residues protein that can be covalently linked to lysine residues on target proteins

41
Q

First step of ubiquitin/proteasome system for protein degradation

A

Poly-ubiquitin tags damaged or misfolded proteins for degradation

42
Q

Second step of ubiquitin/proteasome system for protein degradation

A

Ub tagged proteins are fed into a multisubunit chamber in which each subunit is an inward-facing protease

43
Q

what is E1 and what it does - what drives its reaction

A

Ubiquitin activating enzyme, binds to Ub on carboxyl group (carbonyl group C=O between the two) to activate it. Driven by ATP hydrolysis to AMP (+PPi pyrophosphate release)

44
Q

what is E2 and what it does

A

Ubiquitin-conjugating enzyme. Replaces E1

45
Q

what is E3, what it does and what follows its action

A

Ubiquitin ligase. Helps Ub find misfolded or damaged proteins. After that, poly-ubiquitination can happen (adding of Ubs on the previous Ub to form a chain of Ubs)

46
Q

4 things that happen to Ub tagged protein

A

Recognition by the cap of the proteasome (has 2 caps), deubiquitination, unfolding and degradation under ATP hydrolysis dependent process. (release of peptides)

47
Q

How many E3 genes in human genome and what E3 does specifically

A

100 E3 genes, E3 Ub ligases recognize a variety of chemical side reactions that can occur on amino acids and that aren’t good.

48
Q

2 Exemple of structures that can be recognized by E3 Ub ligases

A

Hydrophobic patches

Oxydized methionine

49
Q

What happens during polyubiquitination

A

Steps 1 (ATP and E1 dependent Ub activation), 2 (E2 replaces E1) and 3 (E3 helps Ub recognize damaged/misfolded protein) are repeated for each Ub that is added

50
Q

Accumulation of misfolded proteins = important aspect of what kind of diseases + 3 ex

A

Neurodegenerative diseases. Parkinson’s, Alzheimer’s and ‘‘mad cow’’ diseases

51
Q

Example of protein responsible for neurodegenerative diseases due to protein misfolding

A

Amyloid precursor that becomes amyloid (what was supposed to become and alpha helix becomes beta-sheet)

52
Q

Why beta-amyloid is bad (2 reasons)

A

Insoluble

Aggregates into filaments that are resistant to proteolysis

53
Q

In what form are amyloid deposits in brain tissue visible in the microscope (2 forms)

A

Plaques

Tangles

Biol 200 (30 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions