Question

Why did the investigators choose amino acids at positions 1, 12, 17, and 18 for modification?

Answer 1

Answer

• So far only serine, threonine and tyrosine amino acid residues have given importance for signal transducion.
• In the case of G-Protein Coupled Receptor (GPCR), the receptor is first activated by the binding of a signal molecule and then further the receptor activates the coupled G-protein by allowing its binding to the receptor and then the signal cascade goes on.
• The initial activation of the receptor (GPCR is a 7 TMS molecule - having 7 transmembrane regions) by a signal molecule can involve certain ion transfer from the signal molecule to the receptor.
• This ion transfer is the basic mechanism of almost all types of signal transduction.
• The best molecule that are involved in the signal transduction are charged amino acids. Theseare abundantly found and are present in all proteins without any exceptions.
• It is already known that basic amino acids such as histidine, arginine and lysine are involved in phosphorylation and thus can be involved in signal ransduction.
• Also such amino acids can be involved in the acid-base proton transfer which can also be a mechanism for the transfer of a signal from one molecule to another.
• Similarly in the above mentioned case histidine (1st amino acid), lysine (12th amino acid) and arginine (17th and 18th amino acid) are basic amino acids, that may be invoved in the tranfer of a signal and thus the activation of the GPCR present on the liver cell membrane.
• Therefore these amino acids must be modified so as to obtain a protein such that it can bind to the GPCR but does not tranduct any signal and thus act as a true antagonist of glucagon.