Question

Describe GPCRs and their function. What atomic-level changes can occur in a ligand or a GPCR, and what are the results from those changes? Describe specific domains and regions of a GPCR and their general function. How are experimental point mutations used to study GPCRs?

Answer 1

1.The G-Protein coupled receptors are the receptors which have seven transmembrane helix.They had an external N terminal that binds to external ligand and transmits the signal to g protein attached to the internal C-terminal.The g protein undergoes a changes as its GDP gets converted to GTP and it gets activated and its activated domain go and binds to target proteins and causes it to undergo the desired changes.

2.The various atomic changes can take place in ligands and GPCR receptor like point mutations or deleation/addition mutations and frameshift mutations.This can lead to changes in binding specificity of the ligand like very tight binding to no binding.In case of GPCRs it can affect its overall structure or the effect on transmitting the intercellual signals or the activation of intermediate G-Protein.

3.

A GPCR receptor consists of external N terminal and middle domain that consists of seven transmembranes so it is a membrane spanning protein transversing it around 7 times.It also has a C terminal domain which is binded by last 7th transmembrane region.The C terminal domain is connected to a g protein which gets activated by a confirmational change when GTP gets exchanged to GDP as ligand binds to the N terminal region.This g protein active its alpha subunit as it is made of three subunits alpha,beta and gamma and only alpha gets seprated on activation and binds to target protein and the changes are observed.

4.The experimental point mutations can be used for eg a null mutant will tell us about the absence of phenotype which can be assigned to g protein.Also mutants will tell us the various domains that are necessary in GPCRs for functioning and which domains mutations will not cause much significant changes.