Kinetic Control of Parallel versus Antiparallel Amyloid Aggregation via Shape of the Growing Aggregate

• Published in: Scientific reports 2019-11, Vol.9 (1), p.15987-12, Article 15987
• Main Authors: Zanjani, Ali Asghar Hakami, Reynolds, Nicholas P., Zhang, Afang, Schilling, Tanja, Mezzenga, Raffaele, Berryman, Joshua T.
• Format: Article
• Language: English
• Subjects: 631/114/2390; 631/45/460; 639/766/94; Aggregates; Amyloid - chemistry; Crystal structure; Crystallography; Design; Humanities and Social Sciences; Kinetics; Lysozyme; multidisciplinary; Peptides; Peptides - chemistry; Physics; Polymorphism; Protein Aggregates; Protein Conformation; Protein Folding; Science; Science (multidisciplinary); Self-assembly; Simulation; Topology; X-Ray Diffraction
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-52238-x

By combining atomistic and higher-level modelling with solution X-ray diffraction we analyse self-assembly pathways for the IFQINS hexapeptide, a bio-relevant amyloid former derived from human lysozyme. We verify that (at least) two metastable polymorphic structures exist for this system which are substantially different at the atomistic scale, and compare the conditions under which they are kinetically accessible. We further examine the higher-level polymorphism for these systems at the nanometre to micrometre scales, which is manifested in kinetic differences and in shape differences between structures instead of or as well as differences in the small-scale contact topology. Any future design of structure based inhibitors of the IFQINS steric zipper, or of close homologues such as TFQINS which are likely to have similar structures, should take account of this polymorphic assembly.