@article{MAKHILLJMG202113128913, title = {A Consensus Sequence among Natural Transmembrane Linkers for Single-Polypeptide Chain (SC) Connection of Two G-Protein-Coupled Receptors in Tandem}, journal = {Journal of Molecular Genetics}, volume = {13}, number = {1}, pages = {1-45}, year = {2021}, issn = {2070-4267}, doi = {jmolgene.2021.1.45}, url = {https://makhillpublications.co/view-article.php?issn=2070-4267&doi=jmolgene.2021.1.45}, author = {Toshio,Takashi,Dasiel Oscar,Haruo and}, keywords = {Transmembrane single polypeptide chain linker,oligomerization,adenosine A2A receptor,dopamine D2 receptor; receptor allostery,fusion protein,striatum,supramolecular protein assembly,consensus sequence of natural scGPCR TM linker}, abstract = {A transmembrane (TM) single-polypeptide chain (sc) linker that can connect any two class A Gprotein- coupled receptors (GPCRs) in tandem as a genefusion strategy has been demonstrated. Here, we report that a natural TM linker for sc exists that can connect two GPCRs in tandem. In silico analysis indicated that the central intervening portion (amino acid residues 311~416) of Exaiptasia diaphana (LOC110241027) GPCR fusion protein contains a single probable TM domain and that a consensus sequence, T(I/A/P) (A/S) (L/N) (I/W/L) (I/A/V) GL (L/G) (A/T) (S/L/G) (I/L) is conserved between this TM and previously characterized TM-linkers deriving from the type II TM proteins with a cytoplasmic N-ter segment, single TM and extracellular C-ter tail, Caenorhabditis elegans odr4 and human CD23. In addition, to the invertebrate TM-linker, it was found that in the central intervening region of tropical bird Opisthocomus hoazin protein LOC104327099 (XP_009930279.1), TM-linker contains the consensus sequence. Here, we directed for the first time, our attention to the natural TM sc linker as a rare evolutionary event among all mammalian and avian proteins.} }