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

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 und...

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Main Authors: 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, Fudong Li
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54548-9
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author 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
Fudong Li
author_facet 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
Fudong Li
author_sort Meili Li
collection DOAJ
description 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.
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spelling doaj-art-cec402e2816d4f738b37af3c3858cc3a2025-08-20T02:51:16ZengNature PortfolioNature Communications2041-17232024-11-0115111610.1038/s41467-024-54548-9Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteinsMeili Li0Chengming Zhu1Zheng Xu2Mingjing Xu3Yan Kuang4Xinhao Hou5Xinya Huang6Mengqi Lv7Yongrui Liu8Yong Zhang9Ziyan Xu10Xu Han11Suman Wang12Yunyu Shi13Shouhong Guang14Fudong Li15MOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaMOE Key Laboratory for Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, The First Affiliated Hospital of USTC, Biomedical Sciences and Health Laboratory of Anhui Province, Division of Life Sciences and Medicine, University of Science and Technology of ChinaAbstract 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.https://doi.org/10.1038/s41467-024-54548-9
spellingShingle 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
Fudong Li
Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteins
Nature Communications
title Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteins
title_full Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteins
title_fullStr Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteins
title_full_unstemmed Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteins
title_short Structural basis for C. elegans pairing center DNA binding specificity by the ZIM/HIM-8 family proteins
title_sort structural basis for c elegans pairing center dna binding specificity by the zim him 8 family proteins
url https://doi.org/10.1038/s41467-024-54548-9
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