由着丝粒蛋白 CENP-C 识别着丝粒核小体的保守机制。
A conserved mechanism for centromeric nucleosome recognition by centromere protein CENP-C.
机构信息
Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.
出版信息
Science. 2013 May 31;340(6136):1110-3. doi: 10.1126/science.1235532.
Abstract
Chromosome segregation during mitosis requires assembly of the kinetochore complex at the centromere. Kinetochore assembly depends on specific recognition of the histone variant CENP-A in the centromeric nucleosome by centromere protein C (CENP-C). We have defined the determinants of this recognition mechanism and discovered that CENP-C binds a hydrophobic region in the CENP-A tail and docks onto the acidic patch of histone H2A and H2B. We further found that the more broadly conserved CENP-C motif uses the same mechanism for CENP-A nucleosome recognition. Our findings reveal a conserved mechanism for protein recruitment to centromeres and a histone recognition mode whereby a disordered peptide binds the histone tail through hydrophobic interactions facilitated by nucleosome docking.
摘要
有丝分裂过程中的染色体分离需要在着丝粒处组装动粒复合物。动粒组装依赖于中心体蛋白 C（CENP-C）对着丝粒核小体中组蛋白变体 CENP-A 的特异性识别。我们已经确定了这种识别机制的决定因素，并发现 CENP-C 结合 CENP-A 尾部的一个疏水区，并与组蛋白 H2A 和 H2B 的酸性斑结合。我们进一步发现，更为广泛保守的 CENP-C 基序使用相同的机制识别 CENP-A 核小体。我们的研究结果揭示了一种用于蛋白招募到着丝粒的保守机制，以及一种组蛋白识别模式，其中无序肽通过核小体对接促进的疏水相互作用结合组蛋白尾部。
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Nat Struct Mol Biol. 2012 Dec;19(12):1218-27. doi: 10.1038/nsmb.2436.
2
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Nat Cell Biol. 2012 May 6;14(6):604-13. doi: 10.1038/ncb2493.
3
Cnn1 inhibits the interactions between the KMN complexes of the yeast kinetochore.Cnn1 抑制酵母动粒的 KMN 复合物之间的相互作用。
Nat Cell Biol. 2012 May 6;14(6):614-24. doi: 10.1038/ncb2495.
4
Structural basis of silencing: Sir3 BAH domain in complex with a nucleosome at 3.0 Å resolution.沉默的结构基础：Sir3 BAH 结构域与核小体复合物的 3.0Å 分辨率结构
Science. 2011 Nov 18;334(6058):977-82. doi: 10.1126/science.1210915.
5
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Curr Opin Struct Biol. 2011 Dec;21(6):744-9. doi: 10.1016/j.sbi.2011.10.001. Epub 2011 Nov 5.
6
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7
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8
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