Three‐dimensional structure and antigenicity of transmembrane‐protein peptides of the human immunodeficiency virus type 1

FEBS Letters

Hilton, Bruce²  Ferretti, James A.⁴  Blomberg, Jonas³  Pipkorn, Rüdiger¹  Klasse, Per Johan³  Han, Kyou-Hoon⁴ 

[1] Replico AB, Lomma, Sweden;Chemical Synthesis and Analysis Laboratory, Program Resources Inc/Dyncorp, NCI-Frederick Cancer Research and Development Center, Frederick, MD 21702, USA;Section of Virology, Department of Medical Microbiology, University of Lund, Lund, Sweden;Laboratory of Biophysical Chemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA

关键词: Antigenic peptide;    3D structure;    Escape mutant;    Human immunodeficiency virus type 1;    A;    alanine;    C;    cysteine;    D;    aspartic acid;    E;    glutamic acid;    G;    glycine;    I;    isoleucine;    K;    lysine;    L;    leucine;    P;    proline;    Q;    glutamine;    R;    arginine;    S;    serine;    T;    threonine;    V;    valine;    W;    tryptophan;    Y;    tyrosine;    NOESY;    nuclear Overhauser effect and exchange spectroscopy;    NMR;    nuclear magnetic resonance;    CD;    circular dichroism spectropolarimetry;   

DOI  :  10.1016/0014-5793(93)81450-E

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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% α-helix coula 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.

【 授权许可】

Unknown