title: Structure of the LAV6 peptide: a nucleation site for the correct receptor-induced refolding of the CD4-binding domain of HIV1 gp 120.
abstract: LAV44 and LAV15 (lymphadenopathy-associated virus) peptides of the CD4-binding region of gp 120 per se bind to the CD4 receptor (Reed and Kinzel, Biochemistry 30: 4521-4528, 1991; Lasky et al., Cell 50:975-985, 1987). Depending on the environment, the LAV peptides exhibit the ability to switch cooperatively between beta-sheet and helical conformation when solvent polarity is changed past a critical point. This property, which is dependent on the amino acid sequence LPCR, is crucial for receptor binding (Reed and Kinzel, Proc. Natl. Acad. Sci. U.S.A. 90:6761-6765, 1993). Structure determination with 2D-NMR-spectroscopy reveals that LAV6 peptide (sequence: TLPCRI) has a well-defined structure, partially exhibiting inverse gamma-turn conformation in aqueous solution. Quantitative evaluation of the NMR data discloses 90% trans-conformation for the peptide bond between leucine and proline. The psi- and phi-angles fall into the typical range for amino acids located in turns. On the other hand, the amino acid sequence C-terminal to the LPCR tetrad has been shown to fold atypically in the absence of these residues. All these results show that the short sequence of LAV6 peptide, with the central amino acids LPCR, displays a matrix-independent structure and may, therefore, act as a conformational template for forming secondary structure in the intact CD4-binding domain of gp 120.
authors.affiliation: Department of Pathochemistry, German Cancer Research Center, Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Lindemann
authors.forename: V
authors.initials: V
authors.lastname: Kinzel
authors.forename: P
authors.initials: P
authors.lastname: Rösch
authors.forename: J
authors.initials: J
authors.lastname: Reed
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D010455:Peptides