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Photoprogramming Allostery in Human Serum Albumin
[Image: see text] 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 selec...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053643/ https://www.ncbi.nlm.nih.gov/pubmed/29975051 http://dx.doi.org/10.1021/acs.bioconjchem.8b00184 |
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author | Putri, Rindia M. Zulfikri, Habiburrahman Fredy, Jean Wilfried Juan, Alberto Tananchayakul, Pichayut Cornelissen, Jeroen J. L. M. Koay, Melissa S. T. Filippi, Claudia Katsonis, Nathalie |
author_facet | Putri, Rindia M. Zulfikri, Habiburrahman Fredy, Jean Wilfried Juan, Alberto Tananchayakul, Pichayut Cornelissen, Jeroen J. L. M. Koay, Melissa S. T. Filippi, Claudia Katsonis, Nathalie |
author_sort | Putri, Rindia M. |
collection | PubMed |
description | [Image: see text] 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. |
format | Online Article Text |
id | pubmed-6053643 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-60536432018-07-22 Photoprogramming Allostery in Human Serum Albumin Putri, Rindia M. Zulfikri, Habiburrahman Fredy, Jean Wilfried Juan, Alberto Tananchayakul, Pichayut Cornelissen, Jeroen J. L. M. Koay, Melissa S. T. Filippi, Claudia Katsonis, Nathalie Bioconjug Chem [Image: see text] 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. American Chemical Society 2018-07-05 2018-07-18 /pmc/articles/PMC6053643/ /pubmed/29975051 http://dx.doi.org/10.1021/acs.bioconjchem.8b00184 Text en Copyright © 2018 American Chemical Society This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License (http://pubs.acs.org/page/policy/authorchoice_ccbyncnd_termsofuse.html) , which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes. |
spellingShingle | Putri, Rindia M. Zulfikri, Habiburrahman Fredy, Jean Wilfried Juan, Alberto Tananchayakul, Pichayut Cornelissen, Jeroen J. L. M. Koay, Melissa S. T. Filippi, Claudia Katsonis, Nathalie Photoprogramming Allostery in Human Serum Albumin |
title | Photoprogramming Allostery in Human Serum Albumin |
title_full | Photoprogramming Allostery in Human Serum Albumin |
title_fullStr | Photoprogramming Allostery in Human Serum Albumin |
title_full_unstemmed | Photoprogramming Allostery in Human Serum Albumin |
title_short | Photoprogramming Allostery in Human Serum Albumin |
title_sort | photoprogramming allostery in human serum albumin |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053643/ https://www.ncbi.nlm.nih.gov/pubmed/29975051 http://dx.doi.org/10.1021/acs.bioconjchem.8b00184 |
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