Cis/trans heterogeneity of Gln30-Pro31 peptide bond determines whether a 79-residue fragment of staphylococcal nuclease self-associates.

The self-association reaction of a 79-residue fragment of staphylococcal nuclease (SNase79) was studied by far-UV CD, size-exclusion chromatography, and heteronuclear multidimensional NMR spectroscopy. A large population of SNase79 is in self-associated state while a small population of SNase79 is essentially in a monomeric state. The sequence region Thr13-Val39 is responsible for association interface of SNase79. The trans-conformation of X-prolyl bond Gln30-Pro31 may make residues Tyr27-Gln30, serve as a folding nucleation site, and lead the segment Thr13-Val39 of SNase79 to adopt a native-like beta-sheet conformation, which results in the self-association of SNase79. The non-native conformation of the segment Thr13-Val39 of SNase79 associated with the cis-conformation of X-prolyl bond Gln30-Pro31 may preclude SNase79 from the soluble aggregates.