Conformational Shift of a β-Hairpin Peptide upon Complex Formation with an Oligo-proline Peptide Studied by Mass Spectrometry.

So-called super-secondary structures such as the β-hairpin, studied here, form an intermediate hierarchy between secondary and tertiary structures of proteins. Their sequence-derived 'pure' peptide backbone conformation is combined with 'remote' interstrand or interresidue contacts reminiscent of the 3D-structure of full-length proteins. This renders them ideally suited for studying potential nucleation sites of protein folding reactions as well as intermolecular interactions. But β-hairpins do not merely serve as model systems; their unique structure characteristics warrant a central role in structural studies on their own. In this study we applied photo cross-linking in combination with high-resolution mass spectrometry and computational modeling as well as with ion mobility-mass spectrometry to elucidate these structural properties. Using variants of a known β-hairpin representative, the so-called trpzip peptide and its ligands, we found evidence for a conformational transition of the β-hairpin and its impact on ligand binding.