Anti-aggregation Properties of the Mini-Peptides Derived from Alpha Crystallin Domain of the Small Heat Shock Protein, Tpv HSP 14.3.

Abstract

The highly conserved alpha crystallin domain of the small heat shock proteins is essential for dimerization and also implicated in substrate interaction. In this study, we designed four novel mini-peptides from alpha crystallin domain of archaeal Small Heat Shock Protein Tpv HSP 14.3. Among the peptide designs, the mini-peptides ₃₈SDLVLEAEMAGFDKKNIKVS₅₇ and ₄₀LVLEAEMAGFD₅₀ overlapped to the sequences of β3-β4 region. The other two peptides ₇₇YIDQRVDKVYKVVKLPVE₉₄ and ₁₀₇GILTVRMK₁₁₄ correspond to β6-β7 region and β9, respectively. Functional activity of the peptides was evaluated by monitoring heat-induced aggregation of the model substrates alcohol dehydrogenase at 43 °C and citrate synthase at 45 °C. Our results showed that the (38-57) and the (77-94) fragments exhibited chaperone activity with both of the substrate proteins. The (40-50) fragment while exhibiting a noticeable protective effect (> 90%) when tested with citrate synthase showed an anti-chaperone property toward alcohol dehydrogenase. Unlike the (40-50) fragment, the (107-114) fragment did not show any chaperone activity with citrate synthase but exhibited the highest chaperone efficiency among four mini-peptides with alcohol dehydrogenase. The selectivity of the (40-50) and the (107-114) fragments in targeting the client proteins is most likely dependent on their surface hydrophobicity and/or charge as revealed by the sequence and exposed surface analyses.