De novo design of self-assembling helical protein filaments

Author:

Shen Hao123ORCID,Fallas Jorge A.12ORCID,Lynch Eric2ORCID,Sheffler William12,Parry Bradley45,Jannetty Nicholas56ORCID,Decarreau Justin7ORCID,Wagenbach Michael7,Vicente Juan Jesus7,Chen Jiajun89ORCID,Wang Lei910,Dowling Quinton211ORCID,Oberdorfer Gustav12ORCID,Stewart Lance1ORCID,Wordeman Linda7,De Yoreo James89ORCID,Jacobs-Wagner Christine5612,Kollman Justin2ORCID,Baker David1213ORCID

Affiliation:

1. Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.

2. Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

3. Molecular Engineering Ph.D. Program, University of Washington, Seattle, WA 98195, USA.

4. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.

5. Microbial Sciences Institute, Yale University, West Haven, CT 06516, USA.

6. Howard Hughes Medical Institute, Yale University, West Haven, CT 06516, USA.

7. Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.

8. Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA.

9. Physical Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA.

10. State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100, China.

11. Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.

12. Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06510, USA.

13. Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.

Abstract

Built to be reversible There has been some success in designing stable peptide filaments; however, mimicking the reversible assembly of many natural protein filaments is challenging. Dynamic filaments usually comprise independently folded and asymmetric proteins and using such building blocks requires the design of multiple intermonomer interfaces. Shen et al. report the design of self-assembling helical filaments based on previously designed stable repeat proteins. The filaments are micron scale, and their diameter can be tuned by varying the number of repeats in the monomer. Anchor and capping units, built from monomers that lack an interaction interface, can be used to control assembly and disassembly. Science , this issue p. 705

Funder

Howard Hughes Medical Institute

Defense Advanced Research Projects Agency

Marie Curie Post-doctoral Research Fellowships

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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