Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteins
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.
Authors
- Fudong Li (ORCID: https://orcid.org/0000-0002-9434-3762)
- Shouhong Guang (ORCID: https://orcid.org/0000-0001-7700-9634)
- Yunyu Shi (ORCID: https://orcid.org/0000-0002-1348-4759)
- Suman Wang
- Xinhao Hou (ORCID: https://orcid.org/0009-0002-3838-6060)
- Meili Li (ORCID: https://orcid.org/0000-0002-2725-3978)
- Yongrui Liu (ORCID: https://orcid.org/0009-0003-9301-7978)
- Mingjing Xu
- Xinya Huang (ORCID: https://orcid.org/0009-0006-1077-1564)
- Yong E. Zhang (ORCID: https://orcid.org/0000-0003-3770-2383)
- Chengming Zhu (ORCID: https://orcid.org/0000-0003-4930-2192)
- Mengqi Lv (ORCID: https://orcid.org/0000-0002-1326-3227)
- Yan Kuang (ORCID: https://orcid.org/0000-0001-9015-991X)
- Ziyan Xu (ORCID: https://orcid.org/0000-0003-3790-2297)
- Zheng Xu (ORCID: https://orcid.org/0000-0002-5374-4121)
- Han Xu (ORCID: https://orcid.org/0000-0002-8654-461X)
Institutions
- University of Science and Technology of China (CN)
- Sichuan University (CN)
- Hefei National Center for Physical Sciences at Nanoscale (CN)
- State Key Laboratory of Biotherapy
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1038/s41467-024-54548-9
- Citations
- 4
- Primary Topic
- DNA Repair Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- Chinese Academy of Sciences
- University of Science and Technology of China
- Fundamental Research Funds for the Central Universities