Sensing the allosteric force

Nature Communications
Olga BozovicPeter Hamm

Abstract

Allosteric regulation is an innate control in most metabolic and signalling cascades that enables living organisms to adapt to the changing environment by tuning the affinity and regulating the activity of target proteins. For a microscopic understanding of this process, a protein system has been designed in such a way that allosteric communication between the binding and allosteric site can be observed in both directions. To that end, an azobenzene-derived photoswitch has been linked to the α3-helix of the PDZ3 domain, arguably the smallest allosteric protein with a clearly identifiable binding and allosteric site. Photo-induced trans-to-cis isomerisation of the photoswitch increases the binding affinity of a small peptide ligand to the protein up to 120-fold, depending on temperature. At the same time, ligand binding speeds up the thermal cis-to-trans back-isomerisation rate of the photoswitch. Based on the energetics of the four states of the system (cis vs trans and ligand-bound vs free), the concept of an allosteric force is introduced, which can be used to drive chemical reactions.

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Citations

Feb 27, 2021·The Journal of Physical Chemistry. B·Tandac F GucluCanan Atilgan
Apr 28, 2021·The Journal of Physical Chemistry Letters·Olga BozovicPeter Hamm
May 18, 2021·Biochemistry·Brankica JankovicPeter Hamm

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Methods Mentioned

BETA
X-ray
circular dichroism
NMR
Fluorescence

Software Mentioned

MicroCal ITC200
MicroCal ITC200 Origin
OriginPro2018b
MassLynx
Origin ITC

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