Analysis of the three dimensional structure of the CXGXC motif in the CMGCC and CAGYC regions of α- and β-subunits of human chorionic gonadotropin: Importance of glycine residue (G) in the motif

The three dimensional structures of the C₁X₂G ₃(X₃)X₄C₅ motif of hCG, which is considered to be important for noncovalent assembly of the α- and β-subunits of glycoprotein hormones were analyzed to assess the importance of glycine (Gly) (G) at site X₃ in the motif by the conformational energy calculation using computational procedures. In the C₁M ₂G₃(X₃)C₄C₅ motif of the α-subunit, Ramachandran plot analysis showing the allowed area of the dihedral angles demonstrated that only a Gly residue was allowed at site X ₃. In calculating collision with surrounding atoms as a monomer the possible main chain models of the C₁A₂G₃(X ₃)Y₄C₅ motif in the β-subunit showed that only alanine (Ala) (A) or Gly at site X₃ is allowed to alleviate the collision with the cysteine (Cys) (C) residues which form a disulfide bridge. A mutant of the β-subunit with the C₁A₂A ₃(X₃)Y₄C₅ motif (Ala at site X ₃) may not compose a heterodimer with the α-subunit because of interference of intermolecular hydrogen bond formation. These findings indicate that the Gly residue at site X₃ (G₃) in the motif is essential for heterodimer formation of glycoprotein hormones. The significance of similar motifs found in various human proteins other than glycoprotein hormones was suggested.