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.
Department of Medical Microbiology, University of Lund, Sweden.
J
J
Klasse
R
R
Pipkorn
J
J
Blomberg
K H
KH
Han
B
B
Hilton
J A
JA
Ferretti
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