Allostery is the process in which the binding of a ligand to a protein at one site induces conformational changes that affect the subsequent binding of a second ligand at another site. Now, a team of researchers from Peking University and Harvard University, led by Xiao-dong Su, Yujie Sun and X. Sunney Xie, has shown that allostery is not restricted to proteins and can occur through DNA. They probed how the unbinding of a protein from double-stranded (ds) DNA was affected by the presence of another protein attached nearby to the same dsDNA molecule.
dsDNA molecules featuring two protein binding sites a defined distance apart were attached to a surface. A fluorescently labelled protein was then attached to one site before a second protein was flowed over the immobilized dsDNA–protein complexes. During this period, the rate of detachment of the initially bound protein was monitored using single-molecule fluorescence. Su, Sun and Xie saw that, on binding, the second protein could either stabilize or destabilize the attachment of the first protein depending on the proximity of the two binding sites. The dependence oscillated with a period of 10 base pairs, that is, if a protein was able to stabilize a second protein 10 base pairs away, it would destabilize a protein if it was 5 base pairs away. 10 is the number of base pairs it takes for dsDNA to complete one helix turn, and so this allosteric behaviour is linked to the structure of dsDNA.
It is suggested that the allostery results from the mechanical properties of the dsDNA. Protein binding generally takes place in the major groove of dsDNA, and molecular dynamics simulations show that the binding of one protein affects the size of the adjacent major groove, widening it or narrowing it (depending on the protein) — again with a periodicity of 10 base pairs. Su, Sun and Xie also demonstrated allostery in the binding of enzymes relevant to transcription and were able to use the effect to modify gene expression in living bacteria.
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Armstrong, G. Appreciating allostery. Nature Chem 5, 251 (2013). https://doi.org/10.1038/nchem.1615
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DOI: https://doi.org/10.1038/nchem.1615