Analysis of the three dimensional structure of the CXGXC motif in the CMGCC and CAGYC regions of alpha-and beta-subunits of human chorionic gonadotropin: importance of glycine residue (G) in the motif.
The three dimensional structures of the C(1)X(2)G (3)(X(3))X(4)C(5) motif of hCG, which is considered to be important for noncovalent assembly of the alpha- and beta-subunits of glycoprotein hormones were analyzed to assess the importance of glycine (Gly) (G) at site X(3) in the motif by the conformational energy calculation using computational procedures. In the C(1)M(2)G (3)(X(3))C(4)C(5) motif of the alpha-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 C(1)A(2)G(3)(X(3))Y(4)C(5) motif in the beta-subunit showed that only alanine (Ala) (A) or Gly at site X(3) is allowed to alleviate the collision with the cysteine (Cys) (C) residues which form a disulfide bridge. A mutant of the beta-subunit with the C(1)A(2)A(3)(X(3))Y(4)C(5) motif (Ala at site X(3)) may not compose a heterodimer with the alpha-subunit because of interference of intermolecular hydrogen bond formation. These findings indicate that the Gly residue at site X(3) (G(3)) 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.
Japan Science Corporation.
Kengo
K
Kinoshita
Masami
M
Kusunoki
Kiyoshi
K
Miyai
D000409:Alanine / Q000032:analysis; D020816:Amino Acid Motifs; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000737:chemistry* / Q000235:genetics*; D003198:Computer Simulation; D003545:Cysteine / Q000032:analysis; D005998:Glycine / Q000032:analysis*; D015292:Glycoprotein Hormones, alpha Subunit / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D018997:Chorionic Gonadotropin, beta Subunit, Human; D015292:Glycoprotein Hormones, alpha Subunit; D003545:Cysteine; D000409:Alanine; D005998:Glycine