FOLDING DYNAMICS AND MECHANISM OF BETA-HAIRPIN FORMATION

Protein chains coil into alpha-helices and beta-sheet structures. Know ing the timescales and mechanism of formation of these basic structura l elements is essential for understanding how proteins fold(1). For th e past 40 years, alpha-helix formation has been extensively investigat ed in synthetic and natural peptides(2-5), including by nanosecond kin etic studies(6,7). In contrast, the mechanism of formation of beta str uctures has not been studied experimentally. The minimal beta-structur e element is the beta-hairpin, which is also the basic component of an tiparallel beta-sheets. Here we use a nanosecond laser temperature-jum p apparatus to study the kinetics of folding a beta-hairpin consisting of 16 amino-acid residues. Folding of the hairpin occurs in 6 mu s at room temperature, which is about 30 times slower than the rate of alp ha-helix formation(6,7). We have developed a simple statistical mechan ical model that provides a structural explanation for this result, Our analysis also shows that folding of a beta-hairpin captures much of t he basic physics of protein folding; including stabilization by hydrog en bonding and hydrophobic interactions, two-state behaviour, and a fu nnel-like, partially rugged energy landscape.