receptor structure and signal transduction Flashcards
name an example of a pentameric, tetrameric and trimeric ligand gated ion channel
pentameric: nAChRs
tetrameric: glutamate receptors e.g NMDA
trimeric: ATP (P2X) receptors
how many transmembrane alpha helices do ligand gated ion channels have
pentameric: 4
tetrameric: 3
trimeric: 2
where are the N and C terminus located for LGICs
pentameric: both N and C are extracellular
tetrameric: N terminus extracellularly C intracellular
trimeric: both intracellular
what are cys loop receptors
pentameric ligand gated ion channels
what time scale to LGICs act over
milliseconds
what 2 main enzymes do GPCRs activate/ inhibit and what second messengers do they produce?
adenylate cyclase: cAMP
phospholipase C: IP3
how many subunits do GPCRs have and how many transmembrane alpha helices?
just 1 subunit/ monomeric
7 transmembrane alpha helices domains
what are G proteins?
heteromeric complexes (alpha beta gamma subunits) which catalyse interconversion of GTP and GDP
what time scale do GPCRs act over
seconds
give three types of examples of signalling molecules that use kinase linked receptors
peptide hormones, growth factors and cytokines
what domains are there in kinase linked receptors and where are the N and C terminus
extracellular ligand binding domain containing N terminus,
single transmembrane domain,
intracellular catalytic effector domain which contains C terminus
give examples of kinase linked receptors
tyrosine kinase receptors and tyrosine kinase linked receptors, insulin receptor
what is the time scale of kinase linked receptors?
hours
what do nuclear receptors do and how do they differ from other receptors?
regulate gene transcription, receptors are soluble
how many regions do intracellular receptors have?
2; DNA binding domain and a ligand binding domain
what happens to intracellular receptors after the ligand binds
the receptors form dimers, the dimeric ligand bound receptor acts as a transcription factor
what is the time scale for intracellular receptors?
hours/ days
how is the therapeutic index calculated?
LD50/ ED50
how many isoforms are there of nAChR subunits?
10 isoforms of alpha
4 isoforms of beta
1 gamma 1 delta 1 epsilon
what happens after a GPCR is activated
ligand binding to receptor causes conformational change which causes G protein to interact with the 3rd intracellular loop
binding of alpha subunit to activated receptor causes GDP to be exchanged for GTP
this causes G protein to be activated and the beta gamma complex dissociates and anchors itself to plasma membrane
GTP bound alpha subunit binds with effector such as adenylate cyclase or phospholipase C
The hydrolysis of GTP causes the alpha subunit to dissociate from effector
what are GAPs
GTPase- activating proteins, regulators of G proteins that speed up hydrolysis of GTP so effects are shortened
what are the different types of G protein
Gs: activates adenylate cyclase and activates calcium channels
Gi: inhibits adenylate cyclase and activates potassium channels
Gq: stimulates phospholipase C, activates potassium channels
Go: stimulates phospholipase C, activates potassium channels, inactivates calcium channels
give examples of the different types of GPCR
Gs: beta adrenoceptor
Gi: alpha 2 adrenoceptor
Gq: alpha 1 adrenoceptor
Go: M2 muscarinic
what happens when agonists bind to kinase linked receptors?
receptor dimerisation
conformational change means active sites are now available to bind ATP which causes autophosphorylation of tyrosine residues
phosphorylated tyrosine residues act as docking sites for effector molecules with src homology domains such as SH2 and SH3 domains, many different effectors may interact with same receptor
where are intracellular receptors located
cytoplasm or nucleus
what are the responses after intracellular receptors are activated
early primary response is synthesis of a few different proteins in primary response, one of these proteins shuts of primary response genes and one of these turns on secondary response genes which produce secondary response proteins
