title: Aggregation properties of a short peptide that mediates amyloid fibril formation in model proteins unrelated to disease.
abstract: 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 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 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 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 selfassembly of the full-length protein. The propensity of peptides to form self-assembled structures that are nonamyloidogenic could be important in potentiating the self-assembly of full-length proteins into amyloid fibrils.
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Chaudhary
authors.forename: Shashi
authors.initials: S
authors.lastname: Singh
authors.forename: Ramakrishnan
authors.initials: R
authors.lastname: Nagaraj
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D002645:Chickens; D002942:Circular Dichroism; D006863:Hydrogen-Ion Concentration; D018625:Microscopy, Atomic Force; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012996:Solutions; D013049:Spectrin / Q000737:chemistry / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D018909:src Homology Domains
chemical_list: D000682:Amyloid; D009842:Oligopeptides; D012996:Solutions; D013049:Spectrin; D019870:1-Phosphatidylinositol 4-Kinase