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In: Biology

The G? subunit is associated with the plasma membrane by a covalently-attached lipid group. Where in...

The G? subunit is associated with the plasma membrane by a covalently-attached lipid group. Where in the cell would targets of G? be located?

Solutions

Expert Solution

G-protein coupled receptors are receptors with seven transmembrane domain, extracellular N terminus and cytoplasmic C terminus, linked to a G protein. The G protein is a trimer of alpha, beta and gamma subunits to form Gα-GDP/Gβγ complex. The Ga subunit is bound to GDP and is attached to plasma membrane by a covalently attached lipid group. When the receptor binds the ligand, a conformation change occurs. The receptor acts as guanine exchange factor and displaces GDP with GTP on G protein alpha subunit. G protein alpha subunit nucleotide pocket is surrounded by three flexible switches that are flexible. These changes in the switches along with binding to GRP will dissociate GTP-bound Gα from Gβγ.

GTP-bound Gα will dissociate from plasma membrane and will bind to adenylyl cyclase. Adenylyl cyclase is attached to the plasma membrane in association with the GPCR. Adenylyl cyclase has binding sites for calcium, magnesium, ATP and GTP. The GTP-bound Gα will bind to adenylyl cyclase via the GTP site. Thus, the immediate target of G alpha is adenylyl cyclse, which is present in the plasma membrane.

Adenylyl cyclase binds to Mg2+ATP and converts it to cAMP. cAMP is released in the cytoplasm. Two cAMP molecules bind to inactive protein kinase A at the regulatory subunits. This causes the catalytic subunits to move out of the regulatory subunits and activates the enzyme. PKA then phosphorylates proteins such as CREB (cyclic AMP response element binding proteins) transcription factor by hydrolysis of ATP. CREB is a cytoplasmic protein that is activated by phosphorylation. Phospho-CREB translocates to the nucleus and binds to CRE (cAMP response elements) on promoter of target genes to activate transcription of target genes. The downstream targets of the G alpha signaling are in cytoplasm and then nucleus. However, the immediate target of G alpha is present in the plasma membrane, which is adenylyl cyclase.


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