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Intrinsic disorder and conformational coexistence in auxin coreceptors

Ramans-Harborough, Sigurd, Kalverda, Arnout P., Manfield, Iain W., Thompson, Gary S., Kieffer, Martin, Uzunova, Veselina, Quareshy, Mussa, Prusinska, Justyna M., Roychoudhry, Suruchi, Hayashi, Ken-ichiro, and others. (2023) Intrinsic disorder and conformational coexistence in auxin coreceptors. Proceedings of the National Academy of Sciences, 120 (40). Article Number e222128612. ISSN 0027-8424. E-ISSN 1091-6490. (doi:10.1073/pnas.2221286120) (KAR id:103099)

Abstract

AUXIN/INDOLE 3-ACETIC ACID (Aux/IAA) transcriptional repressor proteins and the TRANSPORT INHIBITOR RESISTANT 1/AUXIN SIGNALING F-BOX (TIR1/AFB) proteins to which they bind act as auxin coreceptors. While the structure of TIR1 has been solved, structural characterization of the regions of the Aux/IAA protein responsible for auxin perception has been complicated by their predicted disorder. Here, we use NMR, CD and molecular dynamics simulation to investigate the N-terminal domains of the Aux/IAA protein IAA17/AXR3. We show that despite the conformational flexibility of the region, a critical W–P bond in the core of the Aux/IAA degron motif occurs at a strikingly high (1:1) ratio of cis to trans isomers, consistent with the requirement of the cis conformer for the formation of the fully-docked receptor complex. We show that the N-terminal half of AXR3 is a mixture of multiple transiently structured conformations with a propensity for two predominant and distinct conformational subpopulations within the overall ensemble. These two states were modeled together with the C-terminal PB1 domain to provide the first complete simulation of an Aux/IAA. Using MD to recreate the assembly of each complex in the presence of auxin, both structural arrangements were shown to engage with the TIR1 receptor, and contact maps from the simulations match closely observations of NMR signal-decreases. Together, our results and approach provide a platform for exploring the functional significance of variation in the Aux/IAA coreceptor family and for understanding the role of intrinsic disorder in auxin signal transduction and other signaling systems.

Item Type: Article
DOI/Identification number: 10.1073/pnas.2221286120
Additional information: For the purpose of open access, the author(s) has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.
Uncontrolled keywords: IDP, disorder, Aux/IAA, auxin, TIR1
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: Biotechnology and Biological Sciences Research Council (https://ror.org/00cwqg982)
Syngenta (United Kingdom) (https://ror.org/000bdn450)
UK Research and Innovation (https://ror.org/001aqnf71)
Depositing User: Gary Thompson
Date Deposited: 03 Oct 2023 09:14 UTC
Last Modified: 05 Nov 2024 13:09 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/103099 (The current URI for this page, for reference purposes)

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