Photoprogramming Allostery in Human Serum Albumin

Rindia M. Putri, Habiburrahman Zulfikri, Jean Wilfried Fredy, Alberto Juan, Pichayut Tananchayakul, Jeroen J.L.M. Cornelissen, Melissa S.T. Koay, Claudia Filippi* (Corresponding Author), Nathalie Katsonis (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Abstract

Developing strategies to interfere with allosteric interactions in proteins not only promises to deepen our understanding of vital cellular processes but also allows their regulation using external triggers. Light is particularly attractive as a trigger being spatiotemporally selective and compatible with the physiological environment. Here, we engineered a hybrid protein in which irradiation with light opens a new allosteric communication route that is not inherent to the natural system. We select human serum albumin, a promiscuous protein responsible for transporting a variety of ligands in plasma, and show that by covalently incorporating a synthetic photoswitch to subdomain IA we achieve optical control of the ligand binding in subdomain IB. Molecular dynamics simulations confirm the allosteric nature of the interactions between IA and IB in the engineered protein. Specifically, upon illumination, photoconversion of the switch is found to correlate with a less-coordinated motion of the two subdomains and an increased flexibility of the binding pocket in subdomain IB, whose fluctuations are cooperatively enhanced by the presence of ligands, ultimately facilitating their release. Our combined experimental and computational work demonstrates how harnessing artificial molecular switches enables photoprogramming the allosteric regulation of binding activities in such a prominent protein.

Original languageEnglish
Pages (from-to)2215-2224
Number of pages10
JournalBioconjugate chemistry
Volume29
Issue number7
DOIs
Publication statusPublished - 5 Jul 2018

Keywords

  • UT-Hybrid-D

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