Atomic structures of peptide self-assembly mimics

Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17753-8. doi: 10.1073/pnas.0606690103. Epub 2006 Nov 8.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Surface / chemistry*
  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Vaccines / chemistry*
  • Borrelia burgdorferi Group / chemistry
  • Crystallography, X-Ray
  • Lipoproteins / chemistry*
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptides / chemistry*
  • Protein Engineering / methods*
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary
  • Water / chemistry

Substances

  • Antigens, Surface
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Lipoproteins
  • OspA protein
  • Peptides
  • Water

Associated data

  • PDB/2AF5
  • PDB/2FKG
  • PDB/2FKJ
  • PDB/2HKD