Ballesteros-Weinstein Numbering

The Ballesteros-Weinstein numbering system is a generic method of labeling residue numbers in a GPCR. Each of the 7 transmembrane helices in a GPCR contain around the same number of amino acids, however the N-terminus domain varies greatly in length. Since we start usually start numbering from the amino terminus, there is not a consistent number for the first amino acid in a transmembrane alpha helix. Therefore, when we number amino acids conventionally, we do not know the location of a given amino acid in the membrane.

Each transmembrane domain (TMD) 1-7 has an amino acid that is most conserved across all GPCRs, and it is numbered 50. Amino acids are counted backwards moving towards the N-terminus and forward towards the C-terminus. For example, the most conserved amino acid in TMD1 is asparagine, which would be numbered 1-50. An amino acid 4 positions toward the N-terminus would be labeled 1-46, and so on. The most conserved amino acids for each TMD are listed below

TMD1 - Asn (N) TMD5 - Pro (P)

TMD2 - Asp (D) TMD6 - Pro (P)

TMD3 - Arg (R) TMD7 - Pro (P)

TMD4 - Trp (W)

beta2-adrenergic receptor (PDB: 2RH1)

Asn1.50 = N51

Asp2.50 = D79

Arg3.50 = R131

Trp4.50 = W158

Pro5.50 = P211

Pr6.50 = P288

Pro7.50 = P323

PheVIII:04 = F332