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Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17753-8. Epub 2006 Nov 8.

Atomic structures of peptide self-assembly mimics.

Author information

1
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.

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.

PMID:
17093048
PMCID:
PMC1693819
DOI:
10.1073/pnas.0606690103
[Indexed for MEDLINE]
Free PMC Article

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