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 ²¹DIDLHL²⁶ has been shown to be important in the self-assembly of the Src homology 3 (SH3) domain of p85α subunit of bovine phosphatidylinositol-3-kinase (PI3-SH3). The SH3 domain of chicken brain α-spectrin, which is otherwise non-amyloidogenic, is rendered amyloidogenic if ²²EVTMKK²⁷ 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 β-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.