STRUCTURE OF THE LAV6 PEPTIDE - A NUCLEATION SITE FOR THE CORRECT RECEPTOR-INDUCED REFOLDING OF THE CD4-BINDING DOMAIN OF HIV-1 GP-120

LAV44 and LAV15 (lymphadenopathy-associated virus) peptides of the CD4 -binding region of gp 120 per se bind to the CD4 receptor (Reed and Ki nzel, Biochemistry 30: 4521-4528, 1991; Lasky et al., Cell 50:975-985, 1987). Depending on the environment, the LAV peptides exhibit the abi lity to switch cooperatively between beta-sheet and helical conformati on when solvent polarity is changed past a critical point. This proper ty, which is dependent on the amino acid sequence LPCR, is crucial for receptor binding (Reed and Kinzel, Proc. Natl. Acad. Sci, U.S.A. 90:6 761-6765, 1993). Structure determination with 2D-NMR-spectroscopy reve als that LAV6 peptide (sequence: TLPCRI) has a well-defined structure, partially exhibiting inverse gamma-turn conformation in aqueous solut ion. Quantitative evaluation of the NMR data discloses 90% trans-confo rmation for the peptide bond between leucine and proline. The Psi- and Phi-angles fall into the typical range for amino acids located in tur ns. 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 resid ues, All these results show that the short sequence of LAV6 peptide, w ith the central amino acids LPCR, displays a matrix-independent struct ure and may, therefore, act as a conformational template for forming s econdary structure in the intact CD4-binding domain of gp 120. (C) 199 7 Wiley-Liss,Inc.