Lecture 10 - Regulation of Myd88 Dependent Signalling

Question 1

IL-1 Receptor Family and TLRs:

Answer 1

IL-1 Receptor Family:

• Bind IL-1 family members (IL-1, IL-18, IL-33)
• Ig-like extracellular domains (IL-1R, IL-1RAcP)
• Intracellular TIR domain, which recruits Myd88

TLRs:

• Bind PAMPs
• Extracellular Leucine Rich Repeat domain
• Intracellular TIR domain which recruits Myd88 (or in the case of TLR4 or TLR3, recruits Trif)

Question 2

2 main groups of TLRs [by location]:

Answer 2

1. Present on the cell surface: tends to bind bacterial products e.g. LPS
2. Present on the endosome: tends to bind nucleic acids e.g. dsRNA, ssRNA, CpGDNA

Question 3

TLRs activate signalling via which 2 types of signalling?

Answer 3

Myd88 dependent signalling

or

Trif dependent signalling

Question 4

All TLRs, except TLR3, couple via…?

Answer 4

All TLRs, except TLR3, couple via Myd88

Question 5

Does TLR couple via Myd88 or Trif?

[The above TLR should have a number after it, but don’t know which, only one TLR (the above) should couple via Trif (I think)]

Answer 5

Trif

Question 6

TLR2 and TLR4’s recruitment of Myd88 is promoted by a second adaptor called?

Answer 6

Mal

Question 7

TLR4 can couple via both Myd88 and Trif

TRUE OR FALSE

Answer 7

TRUE

Question 8

What mediates the recruitment of Trif to TLR4?

Answer 8

Tram

Question 9

Myd88 Domains:

Answer 9

Death domain: Binds IRAK4 death domain

TIR domain: Binds TIR of intracellular receptor domain

Question 10

The Myddosome is stabilised by?

Answer 10

Interactions between the TIR domains of Myd88, Mal, and TLRs

Interactions between the death domains of IRAKs and Myd88

Question 11

Different BLANK domains recognise different types of polyUbiquitin chains

Answer 11

Different Ubiquitin binding domains recognise different types of polyUbiquitin chains

Question 12

TRAF6 has a RING domain, so catalyses the formation of [Lys63 or Met1?] polyUb chains, in concert with BLANK

Answer 12

TRAF6 has a RING domain, so catalyses the formation of Lys63 polyUb chains, in concert with ubc13 (E2)

Question 13

PolyUb chains formed by BLANK enable downstream signalling by recruitment by Ub chains

Answer 13

PolyUb chains formed by Traf6 enable downstream signalling by recruitment by Ub chains

Question 14

TAK1 complex components:

Answer 14

• Tab2/3
• Tak1
• Tab1

Question 15

M1 chains added to K63 chains by BLANK.

Answer 15

M1 chains added to K63 chains by Lubac (E3)

Question 16

Lubac (E3) components:

Answer 16

HOIP (contains catalytic site)
HOIL
Sharpin

Question 17

K63/M1 hybrid chains promote activation of BLANK

Answer 17

K63/M1 hybrid chains promote activation of IKK

Question 18

IKK complex:

Answer 18

• NEMO
• IKKα
• IKKβ

NEMO contains UBAN domain which recruits IKK complex to M1 chains

IKKα and IKKβ activate NFκB and ERK1/2 pathways

Question 19

Tpl2 is held in an inactive complex with BLANK and BLANK

Answer 19

Tpl2 is held in an inactive complex with p105 and Abin2

Question 20

p105 is phosphorylated by BLANK, targeting it for degradation, freeing Tpl2 to activate BLANK

Answer 20

p105 is phosphorylated by IKKβ, targeting it for degradation, freeing Tpl2 to activate ERK1/2