8JH5

Structure of the auxin exporter PIN1 in Arabidopsis thaliana in the Naproxen-bound state

Summary for 8JH5

• Entry DOI: 10.2210/pdb8jh5/pdb
• EMDB information: 36254
• Descriptor: Auxin efflux carrier component 1, nanobody, (2S)-2-(6-methoxynaphthalen-2-yl)propanoic acid (3 entities in total)
• Functional Keywords: membrane transporter, plant protein
• Biological source: Arabidopsis thaliana (thale cress); More
• Total number of polymer chains: 4
• Total formula weight: 161297.81

Authors

Sun, L.,Liu, X.,Yang, Z.,Xia, J. (deposition date: 2023-05-22, release date: 2024-05-29, Last modification date: 2025-06-11)

Primary citation

Xia, J.,Kong, M.,Yang, Z.,Sun, L.,Peng, Y.,Mao, Y.,Wei, H.,Ying, W.,Gao, Y.,Friml, J.,Weng, J.,Liu, X.,Sun, L.,Tan, S.
Chemical inhibition of Arabidopsis PIN-FORMED auxin transporters by the anti-inflammatory drug naproxen.
Plant Commun., 4:100632-100632, 2023

PubMed Abstract: The phytohormone auxin plays central roles in many growth and developmental processes in plants. Development of chemical tools targeting the auxin pathway is useful for both plant biology and agriculture. Here we reveal that naproxen, a synthetic compound with anti-inflammatory activity in humans, acts as an auxin transport inhibitor targeting PIN-FORMED (PIN) transporters in plants. Physiological experiments indicate that exogenous naproxen treatment affects pleiotropic auxin-regulated developmental processes. Additional cellular and biochemical evidence indicates that naproxen suppresses auxin transport, specifically PIN-mediated auxin efflux. Moreover, biochemical and structural analyses confirm that naproxen binds directly to PIN1 protein via the same binding cavity as the indole-3-acetic acid substrate. Thus, by combining cellular, biochemical, and structural approaches, this study clearly establishes that naproxen is a PIN inhibitor and elucidates the underlying mechanisms. Further use of this compound may advance our understanding of the molecular mechanisms of PIN-mediated auxin transport and expand our toolkit in auxin biology and agriculture.

PubMed: 37254481
DOI: 10.1016/j.xplc.2023.100632

Experimental method

ELECTRON MICROSCOPY (3.7 Å)