1. Atomic structures of peptide self-assembly mimics
- Author
-
Makabe, Koki, McElheny, Dan, Tereshko, Valentia, Hilyard, Aaron, Gawlak, Grzegorz, Yan, Shude, Koide, Akiko, and Koide, Shohei
- Subjects
Protein engineering -- Research ,Peptides -- Structure ,Peptides -- Research ,Science and technology - Abstract
Although the [beta]-rich self-assemblies are a major structural class for polypeptides and the focus of intense research, little is known about their atomic structures and dynamics due to their insoluble and noncrystalline nature. We developed a protein engineering strategy that captures a self-assembly segment in a water-soluble molecule. A predefined number of self-assembling peptide units are linked, and the [beta]-sheet ends are capped to prevent aggregation, which yields a mono-dispersed soluble protein. We tested this strategy by using Borrelia outer surface protein (OspA) whose single-layer [beta]-sheet located between two globular domains consists of two [beta]-hairpin units and thus can be considered as a prototype of self-assembly. We constructed self-assembly mimics of different sizes and determined their atomic structures using x-ray crystallography and NMR spectroscopy. Highly regular [beta]-sheet geometries were maintained in these structures, and peptide units had a nearly identical conformation, supporting the concept that a peptide in the regular [beta]-geometry is primed for self-assembly. However, we found small but significant differences in the relative orientation between adjacent peptide units in terms of [beta]-sheet twist and bend, suggesting their inherent flexibility. Modeling shows how this conformational diversity, when propagated over a large number of peptide units, can lead to a substantial degree of nanoscale polymorphism of self-assemblies. [beta]-sheet | [beta]-strand interaction | amyloid fibril | nanomaterial | protein engineering
- Published
- 2006