Toshio Kamiya, Takashi Masuko, Dasiel Oscar Borroto-Escuela, Haruo Okado, Hiroyasu Nakata,
A Consensus Sequence among Natural Transmembrane Linkers for Single-Polypeptide Chain
(SC) Connection of Two G-Protein-Coupled Receptors in Tandem,
Journal of Molecular Genetics,
Volume 13,Issue 1,
2021,
Pages 1-45,
ISSN 2070-4267,
jmolgene.2021.1.45,
(https://makhillpublications.co/view-article.php?doi=jmolgene.2021.1.45)
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.
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