ESR. 005. Hydrophilic hormones and and enzymes cascades Flashcards
what causes the activation of the G-alpha subunit in a GPCR
hormone bound to receptor cuases exchange of GDP to GTP
what is the structure of a GPCR
7 alpha helices which span the membrane
the G protein part in heterotrimeric
what are the 4 types of G alpha subunit
Gs- activates adenyl cyclase - increasing cAMP
Gi - inhibits adenyl cyclase -reducing cAMP
Gq - activates phospholipase C - increasing DAG, IP3 AND Ca2+
Gt - activates cyclic GMP phosphodiesterase
what type of Ga does the beta adrenergic receptor activate
Gs
what does cAMP do at the beta adrenergic receptor
causes the removal of the regulatory protein off the PKA
how does GTP cause a conformational change in the heterotrimeric G protein
the phosphate on the GTP - has a negative charge and slightly changes the shape of the protein
the switch 2 alpha helix is free now to interact and activate adenyl cyclase
how is the V. cholera toxin harmful on intestinal epithelial cell?
covalently modifies the alpha subunit so it is permanently activated
this works on the Gs so causes lots of adenyl cyclase and so lots of cAMP made
how does the B pertussis toxin affect the cell?
causes AD ribosylation of the Gi subunit - preventing it from interacting with the GPCR - it cannot be activated and therefore have inhibition of the inhibition and loads of cAMP made
what is the structure of protein kinase A
R2C2 hetertetramer
which two amino acids is PKA for
serine and threonine
what is the consensus sequence that PKA recognises
Arg.Arg. X. Ser/Thr. Z
how many cAMPs need to bind to regulatory subunits to make them dissociate from PKA
4
what type of enzyme is tyrosine kinase
receptor enzyme - extracellular ligand binding domain, enzyme active site in intracellular region connected by a single transmembrane segment
eg. insulin receptor
which receptor does epidermal growth factor attach to?
tyrosine kinase
what happens to the receptor after the hormone binds
causes the monomer to expose an interaction site for a homologous recepor
- they can phosphorylate each other
after cross-phorylation which protein binds to the homodimer
Grb-2