通过AAA ATPase Vps4对ESCRT-III进行选择性认可的结构基础
Takayuki Obita1, Suraj Saksena, Sara Ghazi-Tabatabai
1MRC Laboratory of Molecular Biology, Medical Research Council Centre, Cambridge CB2 0QH, UK.
Nature
|October 12, 2007
概括
像Vps4这样的AAA+ ATPase对于细胞功能至关重要. 研究人员发现,特定的Vps4 MIT域与ESCRT-III子单元Vps2和Did2的相互作用对于内体组分类至关重要,并表明古代的进化起源.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- AAA+ ATPase 具有不同的细胞作用,包括膜贩运和蛋白质加工.
- AAA ATPase Vps4对于通过从膜中分解ESCRT复合体来进行内体对 lysosomes的分类,病毒芽生长和细胞分裂至关重要.
研究的目的:
- 阐明Vps4与ESCRT-III子单位相互作用的分子机制.
- 调查Vps4-ESCRT-III伙伴关系的进化起源.
主要方法:
- 确定了与Vps2 C终端复合的Vps4 MIT域的晶体结构.
- 在ESCRT-III子单位内分析了相互作用动机 (D/E) xxxLxxRLxxL ((K/R).
- 确定了一个古老的AAA ATPase N-终端域的晶体结构.
主要成果:
- 只有Vps2和Did2通过它们的C终端30残留绑定Vps4 MIT域.
- 晶体结构显示Vps4 MIT螺旋alpha2和alpha3识别了一个特定的 (D/E)xxLxxRLxxL(K/R) 动图.
- 这种基因的突变导致酵母分类缺陷.
- 一个古老的AAA ATPase的N-终端域在结构上与Vps4 MIT域类似,并与一种ESCRT-III类蛋白相互作用.
结论:
- Vps4-ESCRT-III相互作用是由一个保存的动机介导的,解释了选择性识别.
- 这种Vps4/ESCRT-III的合作关系可能早于真核生物和古生物的分歧,这表明一种古老的保存功能.
- 这种相互作用可能代表了内膜系统进化之前的原始功能的遗迹.
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