Tri-Aspartic Acid Peptides in Water: A Suitable Model System for Determining the Structural Propensities of DxD Motifs in Unfolded Proteins

Abstract

In the context of our ongoing investigations of the conformational propensities of amino acid residues in unfolded peptides we recently focused on the peculiar properties of aspartic acid (D). A detailed spectroscopic study on the tripeptide GDG has shown that D has an unusual preference for turn like structures. This is interesting since D has been shown to be involved in so called asx -turns which are stabilized by hydrogen bonding between the polar residue of e.g. D and the adjacent amide proton. D is also an essential ingredient of DxD motifs which are involved in the enzymatic activity and the Golgi glycosyltransferase GM2. To shed some light on how D-residues behave in D3-motifs we re-investigated the tripeptide D3 with IR, polarized Raman, vibrational circular dichroism, electronic circular dirchroism and NMR spectroscopy. The data are currently being analyzed. First results indicate that D3 has more PPII content than GDG at room temperature and that its actual structure depends on the protonation state of its residues. At high temperature the ECD spectra is indicative of a predominant sampling of right-handed helix or (type III β) turn like conformations, which is rather unexpected. Our results indicate that aspartic acid combines a high degree of plasticity with a preference for turn structures which might explain its role in turn forming segments in proteins and the functional properties of DxD motifs.