Aggregation properties of a short peptide that mediates amyloid fibril formation in model proteins unrelated to disease

Short peptides have been identified from amyloidogenic proteins that form amyloid fibrils in isolation. The hexapeptide stretch (DIDLHL26)-D-21 has been shown to be important in the self-assembly of the Src homology 3 (SH3) domain of p85 alpha subunit of bovine phosphatidylinositol-3-kinase (PI3-SH3). The SH3 domain of chicken brain alpha-spectrin, which is otherwise non-amyloidogenic, is rendered amyloidogenic if (EVTMKK27)-E-22 is replaced by DIDLHL. In this article, we describe the aggregation behaviour of DIDLHL-COOH and DIDLHL-CONH2. Our results indicate that DIDLHL-COOH and DIDLHL-CONH2 aggregate to form spherical structures at pH 5 and 6. At pH 5, in the presence of mica, DIDLHL-CONH2 forms short fibrous structures. The presence of NaCl along with mica results in fibrillar structures. At pH 6, DIDLHL-CONH2 forms largely spherical aggregates. Both the peptides are unstructured in solution but adopt beta-conformation on drying. The aggregates formed by DIDLHL-COOH and DIDLHL-CONH2 are formed during drying process and their structures are modulated by the presence of mica and salt. Our study suggests that a peptide need not have intrinsic amyloidogenic propensity to facilitate the self-assembly of the full-length protein. The propensity of peptides to form self-assembled structures that are non-amyloidogenic could be important in potentiating the self-assembly of full-length proteins into amyloid fibrils.