Computational design of a modular protein sense-response system

Author:

Glasgow Anum A.1ORCID,Huang Yao-Ming1ORCID,Mandell Daniel J.12,Thompson Michael1ORCID,Ritterson Ryan1ORCID,Loshbaugh Amanda L.13ORCID,Pellegrino Jenna13,Krivacic Cody14ORCID,Pache Roland A.1ORCID,Barlow Kyle A.12ORCID,Ollikainen Noah12ORCID,Jeon Deborah1ORCID,Kelly Mark J. S.5ORCID,Fraser James S.136ORCID,Kortemme Tanja12346ORCID

Affiliation:

1. Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.

2. Bioinformatics Graduate Program, University of California San Francisco, San Francisco, CA, USA.

3. Biophysics Graduate Program, University of California San Francisco, San Francisco, CA, USA.

4. UC Berkeley–UCSF Graduate Program in Bioengineering, University of California San Francisco, San Francisco, CA, USA.

5. Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.

6. Quantitative Biosciences Institute, University of California San Francisco, San Francisco, CA, USA.

Abstract

Sense and respond Many signaling pathways start with cellular proteins sensing and responding to small molecules. Despite advances in protein design, creating a protein-based sense-and-respond system remains challenging. Glasgow et al. designed binding sites at the interface of protein heterodimers (see the Perspective by Chica). By fusing each monomer to one half of a split reporter, they linked ligand-driven dimerization to the reporter output. The computational design strategy provides a generalizable approach to create synthetic sensing systems with different outputs. Science , this issue p. 1024 ; see also p. 952

Funder

National Institute of General Medical Sciences

W.M. Keck Foundation

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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