INVOLVEMENT OF THE HIV-1 EXTERNAL ENVELOPE GLYCOPROTEIN-120 (GP120) C2 REGION IN GP120 OLIGOMERIZATION

A synthetic peptide resembling the C2 region of human immunodeficiency virus type 1 (HIV-1) gp120 (C2-Lai: amino acids (aa) 273-288), inhibi ted (C-50 = 200 mu M) gp120 calcium-dependent binding of N-acetyl-beta -D-glucosaminyl and mannosyl residues exposed on natural glycoprotein bovine fetuin whereas a peptide derived from an aa sequence downstream of C2-Lai (C2-SC19) had no such effect (C-50 > 1000 mu M). No calcium -carbohydrate-specific binding of C2-Lai to fetuin was detected. In ad dition, C2-Lai was also found to inhibit the calcium-dependent oligome rization of gp120: while recombinant gp120 (rgp120) was recovered main ly as oligomers (78%) in 10 mM CaCl2, in contrast to 100% monomers in 1 mM CaCl2, mostly monomers (67%) were found in 10 mM CaCl2 in the pre sence of C2-Lai. Peptide C2-SC19 and carbohydrate structures such as f etuin, fucoidin, dextran or mannan did not significantly affect gp120 oligomerization. Electrophoresis and gel filtration analysis also show ed that C2-Lai aggregated in the form of 20 kDa compounds, which is co mpatible with association of 10 molecules. Taken together, these resul ts demonstrate that the C2 domain is involved in gp120 oligomerization and suggest that gp120 oligomers but not monomers have specific carbo hydrate binding properties. (C) 1997 Elsevier Science B.V.