The alpha and omega of G-protein coupled receptors: a novel method for classification. Part 1.

: In this paper, a novel method is presented for classification of 113 neurotransmitter and opioid receptors that is based on the counting of amino acid residues. With the use of sequence alignment, ten conserved key residues were identified: alpha (the first Met residue of the sequence), Asn in the tentative first transmembrane domain (TM1), Asp (TM2), Cys (top of TM3), Arg (bottom of TM3), Trp (TM4), Cys (in the loop between TM4 and TM5), Pro (TM5), Pro (TM6), Pro (TM7) and omega (the last residue of the sequence). The number of residues between these key residues is unique for each receptor or receptor subtype and is used for classification. The number of residues between two key residues defines a segment. The sum of the segments before or after a key residue is defined as a partition. In total, 73 possible classification schemes were found using two or three segments, partitions or a combination of segments and partitions. The surprising and striking results is that each of the sequences examined can be characterized by a code consisting of two or three figures. Each figure represents a number of amino acid residues.