De novo design of tunable, pH-driven conformational changes-Reference-Cited by-同舟云学术

De novo design of tunable, pH-driven conformational changes

Published:2019-05-17 Issue:6441 Volume:364 Page:658-664
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Boyken Scott E.¹²^ORCID,Benhaim Mark A.³^ORCID,Busch Florian⁴^ORCID,Jia Mengxuan⁴,Bick Matthew J.¹²^ORCID,Choi Heejun⁵^ORCID,Klima Jason C.¹²^ORCID,Chen Zibo¹²⁶^ORCID,Walkey Carl¹²,Mileant Alexander³⁶,Sahasrabuddhe Aniruddha⁴,Wei Kathy Y.¹²⁷^ORCID,Hodge Edgar A.³^ORCID,Byron Sarah²^ORCID,Quijano-Rubio Alfredo¹²⁸,Sankaran Banumathi⁹^ORCID,King Neil P.¹²^ORCID,Lippincott-Schwartz Jennifer⁵^ORCID,Wysocki Vicki H.⁴^ORCID,Lee Kelly K.³⁶,Baker David¹²¹⁰^ORCID

Affiliation:

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

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

3. Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.

4. Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.

5. Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA 20147, USA.

6. Graduate Program in Biological Physics, Structure, and Design, University of Washington, Seattle, WA, USA.

7. Department of Bioengineering, University of California, Berkeley, CA 94720, USA.

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

9. Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720.

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

Abstract

Designed to respond Protein design has achieved success in finding sequences that fold to very stable target structures. Protein function, however, often requires conformational dynamics. Boyken et al. describe designed proteins that undergo conformational transitions in response to pH. They designed helical oligomers in which histidines are positioned in hydrogen-bond networks at the interfaces, with complimentary hydrophobic packing around the networks. Lowering the pH protonated the histidine, disrupting the oligomers. After endocytosis into low-pH compartments in cells, the designed proteins disrupted endosomal membranes. Science , this issue p. 658

Funder

National Science Foundation

National Institutes of Health

U.S. Department of Energy

Burroughs Wellcome Fund

Howard Hughes Medical Institute

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference61 articles.

1. Principles that Govern the Folding of Protein Chains