Details

Autor(en) / Beteiligte

• Hoersch, Daniel
• Kortemme, Tanja

Titel

A Model for the Molecular Mechanism of an Engineered Light-Driven Protein Machine

Ist Teil von

• Structure (London), 2016-04, Vol.24 (4), p.576-584

Ort / Verlag

United States: Elsevier Ltd

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Controllable protein-based machines and materials are of considerable interest for diverse biotechnological applications. We previously re-engineered an ATP-driven protein machine, a group II chaperonin, to function as a light-gated nanocage. Here we develop and test a model for the molecular mechanism of the re-engineered chaperonin, which undergoes a large-scale closed to open conformational change triggered by reversible photo-isomerization of a site-specifically attached azobenzene crosslinker. In silico experiments using all-atom simulations suggest that rigid body motions of protein subdomains couple the length changes of the crosslinker to rearrangements of the nucleotide-binding pocket, leading to cage opening. We tested this model by designing a mutant for which the orientation of the two protein subdomains forming the nucleotide-binding pocket is directly controlled by the crosslinker, and confirmed successful reversible photoswitching in vitro. The model probes the conformational cycle of group II chaperonins and offers a design principle for engineering other light-driven protein-based molecular machines. [Display omitted] •In silico study of the mechanism of a re-engineered light-driven chaperonin•Distance- and symmetry-constrained simulations of a 1 MDa protein complex•Model: rotations of the protein subdomains drive the conformational cycle•In vitro experiments support the model Hoersch et al. combine in silico and in vitro experiments to develop and test a model for the conformational cycle of a re-engineered light-driven group II chaperonin. The work sheds light on design principles of protein machines and inspires future engineering of other light-driven nanodevices.