GTP · proteins = Guanosine nucleotide-binding proteins · Functions: 'molecular switches' · Activity regulated by binding and hydrolysis ATP NH2 0 GTP 0 0 0 II NaO-P-O-P-0-P-O- 0 0 O Z Nao-P-O-P-0-P-0. ÓNa 0 O ONa OH OH GTP + protein OH OH NH `NH2 GTP - protein Two types of G-protein signalling 1- Heterotrimeric- G-proteins - · Key signal relay for a large family of serpetine receptors (G protein coupled receptors) Process-
O Hormone Exterior Trimeric Gg protein Inactive receptor Cytosol RESTING STATE 1 Binding of hormone induces a conformational change in receptor O Hormone Active receptor 3 3 GBY G P 2 Activated receptor binds to Gg subunit GBY 3 Activated receptor causes Ga G D P conformational change in Go triggering dissociation of GDP G K 000 G., GB Go G D P Inactive effector P:+ O 6 Hydrolysis of GTP to GDP causes Gq to dissociate from effector and reassociate with GB GpY Active effector 3 Go P 4 5 Hormone dissociates from receptor; Gg binds to effector, activating it O 3 GBY G P 4 Binding of GTP to Ga triggers dissociation of Go both from the receptor and from GBy 3 Figure 15.17 Molecular Cell Biology, Seventh Edition @ 2013 W.H. Freeman and Company 3 GBY Made from: Alpha subunit:40-45 kDa · Ga-subunits are post-translationally modified by myristoylated at N- terminal glycine residue · Myristoylated an irreversible, co-translational (during translation) protein modification of a protein by attachment of a 14 carbon straight chain fatty acidtt In this protein modification, a myristoyl group (derived from myristic acid) is covalently attached via an amide bond to the alpha-amino group of an N-terminal amino acid of a nascent polypeptidett Beta subunit: 35 kDa Gamma subunit: 7kDa · GBy-subunits are post-translationally modified by geranyl /farnesyl side chain · Protein prenylation involves the transfer of either a farnesyl or a geranyl- geranyl moiety to C-terminal cysteine(s) of the target protein, an important process to mediate protein-protein interactions and protein-membrane interactions Where are they located?
Located in cytoplasmic face of the plasma membrane anchoring to the membrane by lipid anchoring-covalentlytt -to dissociate to activate Acetylcholine K+ channel Exterior + + Cytosol GBY Active muscarinic acetylcholine receptor 3 Gazi G D P GTP >GDP K 1 + + + + + 3 Gazi G GBY Figure 15.20 Molecular Cell Biology, Seventh Edition @ 2013 W.H. Freeman and Company · Ga-subunits are post-translationally modified - myristoylation at N-terminal glycine residue: H N CH2 0 Protein · GBy-subunits are post-translationally modified - geranyl/farnesyl side chain S S 3 ZI MN ZI O Exterior NH .* E1 E2 E3 E4 Binding to GPCR At specific regions: TM5,TM6,C6,C4tt H1 H2 H3 H4 (a) Side view B-adrenergic receptor Exterior ligand NH3 (c) B-adrenergic receptor Exterior Cytosol ligand H5 H6 H7 C1 C2 C4 -COO C3 G protein interaction Membrane TM1 Membrane Cytosol TM5 aN Cytosol TM5 TM6 coo- Gas GY GTP GB