Structures and mechanisms of the Arabidopsis cytokinin transporter AZG1 PMID: 38172575

ADC Targets in Oncology

2026-04-10

Structures and mechanisms of the Arabidopsis cytokinin transporter AZG1

Nat Plants. 2024 Jan;10(1):180-191. doi: 10.1038/s41477-023-01590-y.

Lingyi Xu ^# ¹ ² , Wei Jia ^# ³ ⁴ , Xin Tao ^# ⁵ , Fan Ye ⁶ ⁷ , Yan Zhang ⁶ ⁷ , Zhong Jie Ding ⁸ , Shao Jian Zheng ⁸ , Shuai Qiao ⁹ , Nannan Su ⁹ , Yu Zhang ¹⁰ , Shan Wu ¹¹ , Jiangtao Guo ¹² ¹³ ¹⁴ ¹⁵ ¹⁶ ¹⁷

Affiliations

1. Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. [email protected].
2. Nanhu Brain-computer Interface Institute, Hangzhou, China. [email protected].
3. National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, Zhejiang, China.
4. Calibra Lab at DIAN Diagnostics, Key Laboratory of Digital Technology in Medical Diagnostics of Zhejiang Provinces, Hangzhou, Zhejiang, China.
5. State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan, Hubei, China.
6. Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
7. Nanhu Brain-computer Interface Institute, Hangzhou, China.
8. State Key Laboratory of Plant Physiology and Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou, China.
9. International Institutes of Medicine, the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
10. National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, Zhejiang, China. [email protected].
11. State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan, Hubei, China. [email protected].
12. Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. [email protected].
13. Nanhu Brain-computer Interface Institute, Hangzhou, China. [email protected].
14. NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang, China. [email protected].
15. Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. [email protected].
16. Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. [email protected].
17. Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China. [email protected].
# Contributed equally.

Abstract

Cytokinins are essential for plant growth and development, and their tissue distributions are regulated by transmembrane transport. Recent studies have revealed that members of the 'Aza-Guanine Resistant' (AZG) protein family from Arabidopsis thaliana can mediate Cytokinin uptake in roots. Here we present 2.7 to 3.3 Å cryo-electron microscopy structures of Arabidopsis AZG1 in the apo state and in complex with its substrates trans-zeatin (tZ), 6-benzyleaminopurine (6-BAP) or kinetin. AZG1 forms a homodimer and each subunit shares a similar topology and domain arrangement with the proteins of the nucleobase/ascorbate transporter (NAT) family. These structures, along with functional analyses, reveal the molecular basis for Cytokinin recognition. Comparison of the AZG1 structures determined in inward-facing conformations and predicted by AlphaFold2 in the occluded conformation allowed us to propose that AZG1 may carry cytokinins across the membrane through an elevator mechanism.