Engineering extrinsic disorder to control protein activity in living cells

Author:

Dagliyan Onur123,Tarnawski Miroslaw4,Chu Pei-Hsuan3,Shirvanyants David2,Schlichting Ilme4,Dokholyan Nikolay V.12,Hahn Klaus M.3

Affiliation:

1. Program in Molecular and Cellular Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

2. Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

3. Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

4. Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.

Abstract

Engineering control of cellular proteins The ability to switch proteins between active and inactive conformations can give insight into their function. Dagliyan et al. present a method to insert domains that control protein activity. They computationally identified protein loops that are coupled to the active site. Sensory domains inserted into these loops could modulate protein activity when their conformation was changed by light or ligand binding. The authors engineered domains into three different classes of proteins involved in cell signaling and found that switching the proteins between active and inactive states could control the shape and movement of living cells. Science , this issue p. 1441

Funder

NIH

Deutsche Forschungsgemeinschaft

Howard Hughes Medical Institute

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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