Transcript A Model Method to Study Differential G-protein

Winston Sanders
What if the unwanted side effects of
a drug could be diminished while
its medicinal effects amplified?

 Mu Opioid Receptor (MOR)
 Stimulus Trafficking
G-protein Coupled
Receptors (GPCR)

 7-transmembrane protein
 G-protein: Heterotrimeric
Examining the Pathways

Bordetela pertussis toxin (PTX)
-rendered PTX-sensitive Ga (subunit)
proteins unresponsive to GPCR activation
-allowing focused aim towards specific
PTX-insensitive mutant Ga proteins
-Interferes with natural
communication b/w GPCR and G-protein
-Ineffective Mechanism
The Experiment

Inactive
Active!
The Experiment (con’t)

How could desired pathway be
identified?
 Interaction of the Xanthine Nucleotide
Binding Goa Mutant with G Protein-coupled
Receptors
Double Mutant GoaX
The Experiment (con’t)

What were results of GoaX when compared
to wild-type a-subunit?
Activates in same manner!
GoaX conserves natural
responses
Future Hopes

 Use GoaX xanthine binding Ga subunits as efficient
indicators
 Individually transfect specific X-mutant Ga subtypes
with the receptor of interest (MOR)
 Successfully study individual activation pathways