ISSN:
0887-3585
Keywords:
peptide folding
;
NMR
;
gp 120
;
CD4 binding domain
;
inverse γ-turn
;
nucleation site
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Medicine
Notes:
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 β-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 γ-turn conformation in aqueous solution. Quantitative evaluation of the NMR data discloses 90% trans-conformation for the peptide bond between leucine and proline. The Ψ- and Φ-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. Proteins 29:203-211, 1997. © 1997 Wiley-Liss, Inc.
Additional Material:
6 Ill.
Type of Medium:
Electronic Resource
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