Three-dimensional structure and antigenicity of transmembrane-protein peptides of the human immunodeficiency virus type 1. Effects of a neutralization-escape substitution.
A point mutation (Ala-589 to Thr) in the transmembrane protein of the human immunodeficiency virus type 1 (HIV-1) has been shown to decrease the sensitivity of the virus to the neutralizing effect of human HIV-1 specific antibodies [(1990) J. Virol. 64, 3240-3248]. Here 17-residue peptides with the parental and mutant sequences were compared: the parental peptide bound antibodies of sera from HIV-1 infected persons more frequently and with higher affinity than the mutant peptide. However, according to circular dichroism (CD), NMR spectroscopy and molecular modelling the peptides have indistinguishable backbone conformations under a variety of experimental conditions. These techniques showed for both peptides that no ordered helix was present in water solution. However, for both peptides in alcohol-water solutions approximately 60% alpha-helix could be induced. The three-dimensional structures of these peptides provide a basis for understanding how this mutation in the transmembrane protein may affect the interaction with both the outer envelope glycoprotein and with antibodies.
Klasse
J
J
Department of Medical Microbiology, University of Lund, Sweden.
Pipkorn
R
R
Blomberg
J
J
Han
K H
KH
Hilton
B
B
Ferretti
J A
JA
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003198:Computer Simulation; D015686:Gene Products, env / Q000737:chemistry* / Q000276:immunology; D015483:HIV Antibodies / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D015483:HIV Antibodies; C081314:HIV-env (583-599) peptide; D010446:Peptide Fragments; D054299:env Gene Products, Human Immunodeficiency Virus