Lecture 2 | Muscle mechanisms I

Question 1

Muscle in times of trauma/ critical life events

Answer 1

Serves as a protein reservoir, breakdown and use AA to make new proteins

Question 2

Goal proteosome pathway

Answer 2

Well conserved an regulated pathway for protein degradation

Question 3

Enzymes of the proteosome pathway

Answer 3

E1: ubiquitin-activating enzyme
E2: ubiquitin-conjugating enzyme
E3: ubiquitin-protein ligase

Question 4

Steps of the proteosome pathway

Answer 4

1. E3 non-covalently binds to the target protein (specific).
2. E1 activates and binds ubiquitin (requires ATP).
3. Ubiquitin is transferred from E1 to E2.
4. E2 transports ubiquitin to E3 (specific).
5. E3 attaches ubiquitin to the target protein (4x, requires ATP)

• On E1 and E2: bound to sulphate of cysteine
  On target protein: bound to -NH of lysine

Question 5

Tetraubiquitin

Answer 5

Chain of 4 ubiquitin molecules -> mark for degradation

Question 6

Proteasome

Answer 6

In cytosol and nucleus of cells
‘Cap’ recognizes tetraubiquitin
‘Barrow’ unfolds and cleaves protein into smaller peptides (ATP dependent)
Ubiquitin in recycled

Question 7

Proteosome pathway in cachexia

Answer 7

Atrogin-1 and MURF-1 (E3 ligases) are upregulated during inflammation.
Atrogin-1: target proteins involved in muscle protein synthesis and regeneration.
MURF-1: targets muscle proteins itself.

Question 8

N-end rule

Answer 8

The N-terminal AA of a protein determines its half-life.

Assessed by UBR1 and UBR2 (upregulated in cachexia) E3 ligases