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核体表面作为卡波西肉瘤疹病毒LANA的对接站

Andrew J Barbera¹, Jayanth V Chodaparambil, Brenna Kelley-Clarke

¹Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Science (New York, N.Y.)

|February 14, 2006

概括

卡波西的肉瘤相关性疹病毒 (KSHV) 与潜伏相关的核抗原 (LANA) 通过基因组H2A-H2B通过核体结合. 这种相互作用对于病毒基因组与线粒染色体的附着至关重要,揭示了新的KSHV潜伏机制.

科学领域:

病毒学病毒学
分子生物学分子生物学
结构生物学结构生物学

背景情况:

卡波西的肉瘤相关性疹病毒 (KSHV) 在宿主细胞中建立了终身潜伏状态.
在宿主细胞分裂期间维护病毒基因组对于KSHV延迟至关重要.
KSHV延迟关联核抗原 (LANA) 对于将病毒基因组与线性染色体结合至关重要.

研究的目的:

阐明LANA调解病毒基因组附着于线粒体染色体的分子机制.
为了识别参与这种相互作用的特定的组合素成分和LANA区域.
为了确定LANA-核酶体相互作用的结构基础.

主要方法:

位点定向的突变发生,以确定关键的LANA残留物,用于基因素结合和染色体关联.
使用Xenopus精子染色素和复制核细胞的生物化学分析.
进行X射线晶体学以确定LANA-核细胞组合物的结构.

主要成果:

N端的LANA通过组织蛋白H2A-H2B的折叠区域与核体结合.
特定的LANA残留物对于H2A-H2B结合和染色体关联都至关重要.
拉纳不结合H2A-H2B缺乏的Xenopus精子染色体;结合在核细胞复合时恢复.
晶体结构揭示了一个LANA头针与一个参与高阶染色体结构的酸性H2A-H2B区域相互作用.

结论:

核体作为LANA的直接结合平台,调解病毒基因组附着在线粒染色体上.
这种相互作用涉及一个特定的LANA - 基因组H2A-H2B接口,对KSHV延迟至关重要.
这项研究揭示了KSHV延迟的一个新机制,并为核细胞介导蛋白质结合提供了一个范式.

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