Abstract
Cullin RING-type E3 ubiquitin ligases SCFTIR1/AFB1-5 and their AUX/IAA targets perceive the phytohormone auxin. The F-box protein TIR1 binds a surface-exposed degron in AUX/IAAs promoting their ubiquitylation and rapid auxin-regulated proteasomal degradation. Here, by adopting biochemical, structural proteomics and in vivo approaches we unveil how flexibility in AUX/IAAs and regions in TIR1 affect their conformational ensemble allowing surface accessibility of degrons. We resolve TIR1·auxin·IAA7 and TIR1·auxin·IAA12 complex topology, and show that flexible intrinsically disordered regions (IDRs) in the degron’s vicinity, cooperatively position AUX/IAAs on TIR1. We identify essential residues at the TIR1 N- and C-termini, which provide non-native interaction interfaces with IDRs and the folded PB1 domain of AUX/IAAs. We thereby establish a role for IDRs in modulating auxin receptor assemblies. By securing AUX/IAAs on two opposite surfaces of TIR1, IDR diversity supports locally tailored positioning for targeted ubiquitylation, and might provide conformational flexibility for a multiplicity of functional states.
Highlights
Cullin RING-type E3 ubiquitin ligases SCFTIR1/auxin signaling F-box 1–5 (AFB1-5) and their AUX/IAA targets perceive the phytohormone auxin
To evaluate whether structural flexibility is a common feature among AUX/IAAs, we predicted global structural disorder along the sequences of the 29 Arabidopsis thaliana AUX/IAAs in silico (IUPred2A)
We did not know whether these interactions facilitate the formation of the final auxin receptor complex by a twodimensional search on the part of transport inhibitor response 1 (TIR1) on the AUX/IAA surface or vice versa
Summary
Cullin RING-type E3 ubiquitin ligases SCFTIR1/AFB1-5 and their AUX/IAA targets perceive the phytohormone auxin. The F-box protein TIR1 binds a surface-exposed degron in AUX/IAAs promoting their ubiquitylation and rapid auxin-regulated proteasomal degradation. By securing AUX/IAAs on two opposite surfaces of TIR1, IDR diversity supports locally tailored positioning for targeted ubiquitylation, and might provide conformational flexibility for a multiplicity of functional states. In SKP1/CULLIN1/F-BOX PROTEIN (SCF)-type E3 ubiquitin ligases, the interchangeable F-box protein (FBP) determines specificity to the E3 through direct physical interactions with the degradation targets[5,6]. These carry a short degradation signal or degron, located mostly within structurally disordered regions, which is recognized by cognate E3 ligases[7].
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