Membraneless organelles Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

What are membraneless organelles also called?

A

condensates

RNP granules

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

What are membraneless organelles?

A

No phospholipid boundary
protein & RNA
concentrate specific components

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

4 examples of condensates?

A

P bodies - control cell fate
Purinosomes - purine biosynthesis
Nucleoli - ribosome biogenesis
histone locus bodies - mRNA processing

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

What do membraneless organelles behave like?

A

liquid droplets

e.g. P granules drip around nucleus - move to only 1 side to determine cell fate

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

How do droplets coalesce?

A

join together
grow in size over tiem
dynamic reorganisation shown by FRAP

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

Why do molecules form droplets?

A

Reaction crucible
Sequestration
Organisational hub

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

What is LLPS (liquid-liquid phase separation)?

A

Reversible process
protein molecules concentrates in droplets
goes from low entropy to high entropy

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

How can polymer physics be used to explain LLPS?

A

energy of homotypic and heterotypic reactions

When X>0 - phase separation is favoured

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

What parameter can be used to compare energy between the heterotypic and homotypic interactions?

A

Chi parameter

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

What is the critical concentration?

A

above Ccritical - proteins form droplets
below - droplets disperse & dissolve
can modulate Ccritical by posttrans mods, temperature, & ionic strength

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

How do scaffolds help to drive membraneless organelle formation?

A

recruits client proteins/RNAs

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

What is IDR?

A

a functional protein region WITHOUT a unique structure

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

What are SLiMs?

A

short stretches of PROTEIN SEQUENCES that mediate protein-protein INTERACTIONS

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

What are LARKs?

A

Short stretches of PROTEIN SEQUENCES that can BIND weakly to EACH OTHER by forming pair of kinked B-sheets

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

What is multivalent?

A

comprising multiple binding sites for a ligand/protein partner

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

What is Ribonucleoprotein (RNP)?

A

complex of RNA and RNA-binding protein

17
Q

How is LLPS regualted?

A

multivalent interactions between proteins and RNA = drive LLPS

allows molecules to mix together & associate at a high enough concentration to give scaffold structure

18
Q

What determines recruitment to the scaffold

A

more multivalent = more strongly recruited

19
Q

What are the features of proteins that drive membraneless organisation?

A

Stereospecific interactions between well-folded domains

Interactions of SLiMs and well-folded domains

Specific interactions between local structures in IDRs

Promiscuous interactions between IDRs

20
Q

How can phase separation be promoted in cells?

A
  • Change in conc, temp, pH, ionic strength
  • Increasing valency
  • Decreasing solubility - higher propensity to oligomerise or interact with another protein
21
Q

What are post-trans mods that tune LLPS?

A
Lys acetylation
Lys ribosylation 
Arg Methylation
Arg citrullination
Phosphorylation
22
Q

Why is RNA a key player in LLPS?

A

act as scaffold for LLPS
RNA modifications alter structure
increased RNA length can promote LLPS

23
Q

What is membraneless organelle formation driven by?

A

protein OR RNA

increase either protein-protein or RNA-RNA interactions

cause phase separation

24
Q

How do molecules in cells also undergo transitions to the solid state?

A

pathological aggregates
amyloid fibrils
types of plaques

25
Q

What liquid-to-solid transitions are associated with disease?

A

Motor Neurone Disease
Dementia

formation of amyloid fibres

26
Q

What do stress granules contain?

A

mRNA - pre-initiation complexes
translation initiation factors
RNA-binding proteins & non-RNA-binding proteins

27
Q

What do stress granules do?

A

control utilisation of mRNA during stress

implicated in diseases e.g. cancer, neurodegeneration

28
Q

How are stress granules assembled?

A

40S 60S ribosome association with mRNA

puromycin promotes SG formation by stalling transcription

60S subunit falls off

mRNA-40S complex associates with RNA binding proteins that nucleate SG formation

29
Q

How is stress granule assembly regulated?

A

form pre-initiation complex by recognition by eIF-4F complex and joining to eIF2 complex

30
Q

Why does inhibiting translation promote SG formation?

A

inhibits the mTOR pathway

31
Q

What happens to nuclear proteins in dementia patients?

A

proteins leave nucleus
become phosphorylated = do not go back into nucleus
proteins form amyloid fibrils

32
Q

What is a key RBP involved in neurodegenerative disease?

A

TDP43

33
Q

How does phase separation play a role in neurodegeneration?

A

RNP granule dynamicity

Trapping of cellular factors

34
Q

How does phase separation play a role in cancer?

A

cellular signalling transcription

35
Q

How does phase separation play a role in infectious diseases?

A

virus replication
cellular stress response
innate immune response
dormancy of bacteria/fungi

36
Q

What is the key protein that assembles rotavirus factories?

A

NSP5

37
Q

How does phase-separation affect SARS-CoV-2?

A
Nucleocapsid protein (N) undergoes phase separation with RNA 
Small molecules that bind N modulate droplet properties