Symmetry‐Directed Self‐Assembly of a Tetrahedral Protein Cage Mediated by de Novo‐Designed Coiled Coils

Abstract

The organization of proteins into new hierarchical forms is an important challenge in synthetic biology. However, engineering new interactions between protein subunits is technically challenging and typically requires extensive redesign of protein–protein interfaces. We have developed a conceptually simple approach, based on symmetry principles, that uses short coiled‐coil domains to assemble proteins into higher‐order structures. Here, we demonstrate the assembly of a trimeric enzyme into a well‐defined tetrahedral cage. This was achieved by genetically fusing a trimeric coiled‐coil domain to its C terminus through a flexible polyglycine linker sequence. The linker length and coiled‐coil strength were the only parameters that needed to be optimized to obtain a high yield of correctly assembled protein cages.

Document Details

Document Type
Pub Defense Publication
Publication Date
Aug 29, 2017
Source ID
10.1002/cbic.201700406

Entities

People

  • Aaron Sciore
  • Ajitha S. Cristie‐david
  • Brandon T. Ruotolo
  • James C. A. Bardwell
  • Joseph D. Eschweiler
  • Min Su
  • Neil Marsh
  • Philipp Koldewey
  • Somayesadat Badieyan

Organizations

  • Army Research Office
  • Howard Hughes Medical Institute
  • University of Michigan

Tags

Readers

  • Molecular and Cellular Biochemistry
  • Nanocomposite Materials Science
  • Systems Analysis and Design

Technology Areas

  • Biotechnology