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ZIM/HIM-8 家族蛋白介导的秀丽隐杆线虫配对中心 DNA 结合特异性的结构基础。

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

机构信息

MOE 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 China, Hefei, China.

Division of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Nat Commun. 2024 Nov 28;15(1):10355. doi: 10.1038/s41467-024-54548-9.

DOI:10.1038/s41467-024-54548-9
PMID:39609407
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11605055/
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.

摘要

配对中心 (PC) 位于秀丽隐杆线虫每条染色体上，对于同源染色体配对和起始联会至关重要。在每个 PC 内，11/12bp DNA 基序簇招募四个同源的减数分裂特异性蛋白之一：ZIM-1、ZIM-2、ZIM-3 或 HIM-8。然而，ZIM/HIM-8-PC DNA 相互作用特异性的机制基础仍然难以捉摸。在这里，我们描述了 HIM-8、ZIM-1 和 ZIM-2 DNA 结合结构域 (ZF1、ZF2 和 CTD) 分别与它们同源的 PC DNA 基序复合物的晶体结构。这些结构表明 ZF1-2-CTD 折叠为一个集成的结构单元，对于其 DNA 结合特异性至关重要。碱基特异性 DNA 接触残基仅分布在 ZF1-2 上，高度保守。此外，CTD 可能有助于 ZF1-2 的构象多样性，赋予其对不同 PC DNA 基序的结合特异性。这些发现揭示了 ZIM/HIM-8 蛋白识别 PC DNA 基序的机制，表明 PC DNA 基序和 ZF1-2-CTD 之间存在共同进化关系，共同塑造了特异性识别。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/619220cb2af1/41467_2024_54548_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/2170318da624/41467_2024_54548_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/40993765a164/41467_2024_54548_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/62702da76921/41467_2024_54548_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/ef5e4525d8ee/41467_2024_54548_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/711c530941c0/41467_2024_54548_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/c65a18dd9600/41467_2024_54548_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/dcd760db5d7c/41467_2024_54548_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/619220cb2af1/41467_2024_54548_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/2170318da624/41467_2024_54548_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/40993765a164/41467_2024_54548_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/62702da76921/41467_2024_54548_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/ef5e4525d8ee/41467_2024_54548_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/711c530941c0/41467_2024_54548_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/c65a18dd9600/41467_2024_54548_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/dcd760db5d7c/41467_2024_54548_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/192a/11605055/619220cb2af1/41467_2024_54548_Fig8_HTML.jpg

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