molecular basis of graves

Question 1

2 parts of TSH structure and function

Answer 1

a subunit -

B subunit - give the specific function

Question 2

what is TSH receptor

Answer 2

GCPR

Question 3

what are 2 main parts of TSHR

Answer 3

a unit - outer part

B unit - membrane bound aspect

Question 4

what are 3 parts of a unit on TSHR

Answer 4

1. LRD region where TSH binds

2. C region of 50 AA that can be cleaved off by enzymes

Question 5

what is 2 state model for TSHR

Answer 5

1. closed conformation - inactive and can’t be bound

2. Open conformation - satbilized by TSH binding

Question 6

what happens if have mutations at or near stabilizing reagions of TSHR

Answer 6

loss of closed conformation meaning it becomes always active

Question 7

what happens in graves disease

Answer 7

1. TSRH attacked by protease and C peptide is lost
2. reduction of disulfide bridges realsease a subunit
3. freed a units stim. antibodies
4. antibodies then mimic TSH and get hyper thyroidism

Question 8

what are the 2 stimulatory pathways influenced by TSH

Answer 8

1. GsA - GCPR

2. GqA - PLC and IP3

Question 9

what is GsA pathway

Answer 9

1. binding activated adenayn cyclase
2. ATP to cAMP
3. cAMP binds to PKA
4. PKA activates specific protein

Question 10

what is GqA pathway

Answer 10

1. TSHR activation activates phospholipae C via GTP
2. PLC conversion of PIP2 to DAG and IP3
3. IP3 promotes Ca release from ER
4. Ca and DAG activate PKC
5. PKC phosphorylates other proteins