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Flashcards in Protein Dynamics 1 Deck (27):
1

What are chemical shifts defined by in IDPs?

Their sequence.

2

What program is used to predict the chemical shifts of IDPs?

CamCoil

3

What does CamCoil do?

Defines how much the actual IDP has deviated from the ultimate random coil - identifies amounts of secondary structure in proteins.

4

What is Gab2 involved in?

Cellular signalling.

5

Why are IDPs important in cellular signalling?

Can form lots of protein-protein interactions.

6

Describe the structure of Gab2/

Very large - small helical domain (120aa) and rest of protein is disordered.

7

Give examples of proteins Gab2 mediates interactions between.

Tyrosine kinase, GCPRs, cytokine receptor, multi chain immune recognition and integrins.

8

Upon stimulation what can Gab2 interaction with?

Grb2

9

What does Gab2 do after interacting with Grb2?

Recruits SH2 domain containing molecules (e.g. tyrosine phosphatase/PI3K) to activate signalling pathways.

10

What domains does Grb2 contain?

Two SH3 domains (proline rich) and one SH2 domain (tyrosine phosphorylated sequences).

11

What happens upon binding of Gab2 to Grb2 via its SH3 domain?

Gab2 folds.

12

What does Gab2 fold into?

Poly-proline helix once bound.

13

What method was used to characterise the disorderd Gab2 protein?

NMR.

14

What was discovered about Gab2 structure when studied by NMR?

There is residual secondary structure of beta sheets and poly proline helix.

15

What did this residual secondary structure tell you about Gab2?

Showed that the bound state conformation was semi-present in the disordered state - prone to adopt this conformation.

16

What protein is associated with Parkinson's?

Alpha-synuclein

17

What happens to alpha synuclein to cause Parkinson's?

Amyloid.

18

What are the amyloids formed in?

Lewy bodies - inclusion bodies.

19

What do these amyloids do?

Kill neurones in the brain.

20

What is the difference between membrane bound and solution form?

Membrane bound - active form, thought to be helical.
Solution - disordered - not naturally found like this.

21

What is the suggested function of alpha synuclein?

Involved in neurotransmitted release in synaptic cleft.

22

Are some membranes more likely trigger aggregation of alpha synuclein?

Yes.

23

What kind of helix is in alpha synuclein?

Amphipathic.

24

What can be used to monitor transition from disordered protein to membrane bound protein?

Circular Dichroism.

25

Is a portion of the protein still disordered in membrane bound form?

Yes.

26

What is the disordered part of the protein?

Protein-protein interactions - SNARE formation cannot occur if protein is truncated.

27

What is used to probe transient interactions?

Paramagnetic relaxation enhancement in solid state NMR.