De novo design of self-assembling helical protein filaments

Hao Shen, Jorge A Fallas, Eric Lynch, William Sheffler, Bradley Parry, Nicholas Jannetty, Justin Decarreau, Michael Wagenbach, Juan Jesus Vicente, Jiajun Chen, Lei Wang, Quinton Dowling, Gustav Oberdorfer, Lance Stewart, Linda Wordeman, James De Yoreo, Christine Jacobs-Wagner, Justin Kollman, David Baker

Research output: Contribution to journalArticle

Abstract

We describe a general computational approach to designing self-assembling helical filaments from monomeric proteins and use this approach to design proteins that assemble into micrometer-scale filaments with a wide range of geometries in vivo and in vitro. Cryo-electron microscopy structures of six designs are close to the computational design models. The filament building blocks are idealized repeat proteins, and thus the diameter of the filaments can be systematically tuned by varying the number of repeat units. The assembly and disassembly of the filaments can be controlled by engineered anchor and capping units built from monomers lacking one of the interaction surfaces. The ability to generate dynamic, highly ordered structures that span micrometers from protein monomers opens up possibilities for the fabrication of new multiscale metamaterials.

Original languageEnglish
Pages (from-to)705-709
Number of pages5
JournalScience
Volume362
Issue number6415
DOIs
Publication statusPublished - 9 Nov 2018
Externally publishedYes

Keywords

  • Computational Biology/methods
  • Cryoelectron Microscopy
  • Escherichia coli
  • Protein Conformation, alpha-Helical
  • Protein Engineering/methods
  • Protein Folding
  • Protein Structure, Secondary
  • Proteins/chemistry

Fields of Expertise

  • Human- & Biotechnology

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