BetaCore a designed water soluble four-stranded antiparallel β-sheet protein

摘要

BetaCore is a designed ∼50-residue protein in which two BPTI-derived core modules, CM I and CM II, are connected by a 22-atom cross-link. At low temperature and pH 3, homo- and heteronuclear NMR data report a dominant folded (`f') conformation with well-dispersed chemical shifts, i, i+1 periodicity, numerous long-range NOEs, and slowed amide hydrogen isotope exchange patterns that is a four-stranded antiparallel β-sheet with nonsymmetrical and specific association of CM I and CM II. BetaCore `f' conformations undergo reversible, global, moderately cooperative, non-two-state thermal transitions to an equilibrium ensemble of unfolded `u' conformations. There is a significant energy barrier between `f' and `u' conformations. This is the first designed four-stranded antiparallel β-sheet that folds in water.