Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteins

Meili Li, Chengming Zhu, Zheng Xu, Mingjing Xu, Yan Kuang, Xinhao Hou, Xinya Huang, Mengqi Lv, Yongrui Liu, Yong Zhang, Ziyan Xu, Xu Han, Suman Wang, Yunyu Shi (), Shouhong Guang () and Fudong Li ()
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Meili Li: University of Science and Technology of China
Chengming Zhu: University of Science and Technology of China
Zheng Xu: Sichuan University
Mingjing Xu: University of Science and Technology of China
Yan Kuang: University of Science and Technology of China
Xinhao Hou: University of Science and Technology of China
Xinya Huang: University of Science and Technology of China
Mengqi Lv: University of Science and Technology of China
Yongrui Liu: University of Science and Technology of China
Yong Zhang: University of Science and Technology of China
Ziyan Xu: University of Science and Technology of China
Xu Han: University of Science and Technology of China
Suman Wang: University of Science and Technology of China
Yunyu Shi: University of Science and Technology of China
Shouhong Guang: University of Science and Technology of China
Fudong Li: University of Science and Technology of China

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Pairing center (PC) on each chromosome of Caenorhabditis elegans is crucial for homolog pairing and initiating synapsis. Within each PC, clusters of 11/12 bp DNA motif recruit one of four paralogous meiosis-specific proteins: ZIM-1, ZIM-2, ZIM-3, or HIM-8. However, the mechanistic basis underlying the specificity of ZIM/HIM-8-PC DNA interaction remains elusive. Here, we describe crystal structures of HIM-8, ZIM-1 and ZIM-2 DNA binding domains (ZF1, ZF2 and CTD) in complex with their cognate PC DNA motifs, respectively. These structures demonstrated the ZF1-2-CTD folds as an integrated structural unit crucial for its DNA binding specificity. Base-specific DNA-contacting residues are exclusively distributed on ZF1-2 and highly conserved. Furthermore, the CTD potentially contributes to the conformational diversity of ZF1-2, imparting binding specificity to distinct PC DNA motifs. These findings shed light on the mechanism governing PC DNA motif recognition by ZIM/HIM-8 proteins, suggesting a co-evolution relationship between PC DNA motifs and ZF1-2-CTD in shaping the specific recognition.

Date: 2024
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DOI: 10.1038/s41467-024-54548-9

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