Tomographic docking suggests the mechanism of auxin receptor TIR1 selectivity

Veselina Uzunova, Mussa Quareshy, Charo del Genio, Richard Napier

Research output: Contribution to journalArticle

7 Citations (Scopus)
15 Downloads (Pure)

Abstract

We study the binding of plant hormone IAA on its receptor TIR1 introducing a novel computational method that we call tomographic docking and that accounts for interactions occurring along the depth of the binding pocket. Our results suggest that selectivity is related to constraints that potential ligands encounter on their way from the surface of the protein to their final position at the pocket bottom. Tomographic docking helps develop specific hypotheses about ligand binding, distinguishing binders from non-binders, and suggests that binding is a three-step mechanism, consisting of engagement with a niche in the back wall of the pocket, interaction with a molecular filter which allows or precludes further descent of ligands, and binding on the pocket base. Only molecules that are able to descend the pocket and bind at its base allow the co-receptor IAA7 to bind on the complex, thus behaving as active auxins. Analyzing the interactions at different depths, our new method helps in identifying critical residues that constitute preferred future study targets and in the quest for safe and effective herbicides. Also, it has the potential to extend the utility of docking from ligand searches to the study of processes contributing to selectivity.
Original languageEnglish
Article number160139
JournalOpen Biology
Volume6
DOIs
Publication statusPublished - 19 Oct 2016

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Indoleacetic Acids
Ligands
Plant Growth Regulators
Herbicides
Computational methods
Binders
Membrane Proteins
Molecules

Bibliographical note

Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

Copyright © and Moral Rights are retained by the author(s) and/ or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This item cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder(s). The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders.

Keywords

  • Tomographic docking
  • Auxin
  • Receptor selectivity
  • Molecular filter

Cite this

Tomographic docking suggests the mechanism of auxin receptor TIR1 selectivity. / Uzunova, Veselina; Quareshy, Mussa; del Genio, Charo; Napier, Richard.

In: Open Biology, Vol. 6, 160139, 19.10.2016.

Research output: Contribution to journalArticle

Uzunova, Veselina ; Quareshy, Mussa ; del Genio, Charo ; Napier, Richard. / Tomographic docking suggests the mechanism of auxin receptor TIR1 selectivity. In: Open Biology. 2016 ; Vol. 6.
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