Optical control of protein-protein interactions via blue light-induced domain swapping.

Optical control of protein-protein interactions via blue light-induced domain swapping.
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DOI:
10.1021/bi500622x
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发表时间:
2014-08-05
期刊:
影响因子:
2.9
通讯作者:
Woolley, G. Andrew
Woolley, G. Andrew
中科院分区:
生物学3区
文献类型:
--
作者:
Reis, Jakeb M.;Burns, Darcy C.;Woolley, G. Andrew

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The design of new optogenetic tools for controlling protein function would be facilitated by the development of protein scaffolds that undergo large, well-defined structural changes upon exposure to light. Domain swapping, a process in which a structural element of a monomeric protein is replaced by the same element of another copy of the same protein, leads to a well-defined change in protein structure. We observe domain swapping in a variant of the blue light photoreceptor photoactive yellow protein in which a surface loop is replaced by a well-characterized protein–protein interaction motif, the E-helix. In the domain-swapped dimer, the E-helix sequence specifically binds a partner K-helix sequence, whereas in the monomeric form of the protein, the E-helix sequence is unable to fold into a binding-competent conformation and no interaction with the K-helix is seen. Blue light irradiation decreases the extent of domain swapping (from Kd = 10 μM to Kd = 300 μM) and dramatically enhances the rate, from weeks to <1 min. Blue light-induced domain swapping thus provides a novel mechanism for controlling of protein–protein interactions in which light alters both the stability and the kinetic accessibility of binding-competent states.
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