Abstract
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 C1M2G 3(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 X3. In calculating collision with surrounding atoms as a monomer the possible main chain models of the C1A2G3(X3)Y4C 5 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 C1A2A3(X3)Y4C 5 motif (Ala at site X3) 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.
