Targeted destruction of the HIV-1 coat protein gp41 by a catalytic antibody light chain.
Generation of antibodies with the ability to destroy targeted viral coat proteins or tumor antigens is an important aim in current research aimed at developing superior catalytic antibodies. To this end, we raised a monoclonal antibody against a discrete sequence of the envelope gp41, RGPDRPEGIEEEGGERDRD, which is a highly conserved sequence in many human immunodeficiency virus (HIV)-1 strains. The light chain subunit of this antibody catalytically decomposed the targeted peptide antigen. The degradation of the immunized peptide antigen by the light chain was initiated by the hydrolytic scission of the peptide bond between Glu12-Gly13, followed by the successive cleavage reactions of the additional peptic bonds into small peptides and amino acids. The decomposition by the light chain obeyed Michaelis-Menten kinetics (k(cat)/K(m) = 2. 8 x 10(5) M(-1) min(-1)). A characteristic feature of the reaction was a slow initial degradation step, followed by an increase in the rate of catalysis. Removal of the light chain by immunoadsorption at either stage of the reaction resulted in recession of catalysis. The light chain also cleaved recombinant gp41 molecule, but did not degrade proteins unrelated in the sequence to the peptide immunogen (bovine and human serum albumins).
Hifumi
Emi
E
School of Biosciences, Hiroshima Prefectural University, Shobara, Hiroshima-ken 727-0023, Japan.
Mitsuda
Yukie
Y
Ohara
Kyoko
K
Uda
Taizo
T
D000595:Amino Acid Sequence; D017151:Antibodies, Catalytic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001483:Base Sequence; D018076:DNA, Complementary; D015483:HIV Antibodies / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019302:HIV Envelope Protein gp160 / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D017422:Sequence Analysis, DNA; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D007147:Immunoglobulin Light Chains; D012710:Serum Albumin, Bovine