Hello Mohammad Sibtain Kadri

The putative seven-TM structure is considered as the molecular fingerprint shared by all known GPCRs.

The GPCR superfamily is evolutionarily conserved and structurally characterized by possessing seven-transmembrane (TM) domains with an extracellular N terminus and a cytoplasmic C terminus. The universal adoption of the conserved seven-TM structure by GPCRs, which consequently confers three intracellular and three extracellular loops along with a TM core, generally is speculated as the minimum necessity to achieve their structural stability and functional diversity. For instance, when activated by the appropriate ligands, most GPCRs can usually recognize and activate more than one G protein but interact with only a distinct subset of the many structurally similar G proteins that are expressed in a cell.

Structural information encoded by the receptor and G-protein amino acid sequences is the primary basis for receptor–G protein recognition. Coupling to a G protein responsible for a particular effect on an intracellular signaling pathway requires a specific structure in the cytoplasmic loops and C-terminal region of the GPCR. For example, inhibition of adenylate cyclase by activation of the Gi protein requires a long third cytoplasmic loop and a short C-terminal region, whereas stimulation of phosphoinositide hydrolysis via the Gq protein requires a short third cytoplasmic loop and a long C-terminal region.

None of the nearly 2,000 GPCRs identified in prokaryotes and eukaryotes to date is known to contain fewer than seven TM domains.

However, the paper attached below, suggests the possible existence of functional GPCRs with five-TM domains. The chemokine receptors with only five TMs which appear to act as functional GPCRs in the aspects of receptor expression, signaling, internalization, and desensitization has been reported. The data obtained from this study suggests that the five-TM domain structure appears to be sufficient for a functional GPCR, at least in the cases of CCR5 and CXCR4. The five-TM chemokine receptors CCR5 and CXCR4 function in many aspects tested indistinguishably from their seven-TM counterparts and indicate that the five-TM structure is feasible within the chemokine receptor family.

Article Five-transmembrane domains appear sufficient for a G protein...

As per your suggestion, I feel that reducing the number to three would be insufficient to form a stable, flexible, TM core. It is important to know that the structure and function relationship of GPCRs plays an importance role in the regulation of numerous cellular functions.

Best.

Yes, I go with you even though my answer is similar to yours, and I state as follows:

No, because seven segments of G-protein coupled receptors (GPCRs) molecule span the entire membrane width, explaining why GPCRs are sometimes called seven-transmembrane receptors and the intervening portions loop both inside and outside the cell. Therefore, if the number of its trans-membrane domains is reduced to three, its function will change, and it will no longer detect molecules outside the cell and activate cellular responses. Malcolm Nobre

Is there any study showed that reduction to three is of beneficial value?

No.