SOLVENT POLARITY-DEPENDENT STRUCTURAL REFOLDING - A CD AND NMR-STUDY OF A 15 RESIDUE PEPTIDE

A close association between the HIV surface protein gp120 and the CD4 T cell receptor initiates the viral multiplication cycle. A 15 amino a cid peptide (LAV) within the CD4 binding domain of gp 120 has been sho wn to retain receptor binding ability. The structural behavior of the LAV peptide has been studied by CD and NMR methods in aqueous solution and upon addition of trifluoroethanol (TFE) to emulate the relatively apolar conditions at the membrane bound receptor. Previous work has s hown that the LAV peptide folds into a P-pleated structure in more pol ar buffer/ TFE mixtures, while a concerted structural change can be ob served at a concentration of 60% TFE (v/v). This abrupt, cooperative r efolding from a regular beta-sheet to a helical secondary structure is known as ''switch'' behavior. Former CD experiments with LAV sequence variants have supported the assumption that four amino acids at the N -terminus (LPCR) are indispensable for the ''switch.'' The tetrad has a strong beta-turn forming potential. The suggestion has been formulat ed that the tetrad can act as a nucleation site governing the refoldin g. The present NMR study of the LAV peptide in TFE gives evidence for a 3(10)-helix suggesting that the tetrad adopts a type III beta-turn a nd promotes the formation of a similar bend in the next overlapping te trad until the sequence is restructured into a 3(10)-helix at a critic al polarity favoring intrachain hydrogen bonds. (C) 1995 Wiley-Liss, I nc.