Structural Basis of Molecular Recognition between ESCRT-III-like Protein Vps60 and AAA-ATPase Regulator Vta1 in the Multivesicular Body Pathway*♦
Structural Basis of Molecular Recognition between ESCRT-III-like Protein Vps60 and AAA-ATPase Regulator Vta1 in the Multivesicular Body Pathway*♦
复制标题
DOI：
10.1074/jbc.m112.390724
复制
发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Zhongzheng Yang;C. Vild;J. Ju;Xu Zhang;Jianping Liu;Jie Shen;Bin Zhao;W. Lan;F. Gong;Maili Liu;C. Cao;Zhaohui Xu
中科院分区：
文献类型：
--
作者：
Zhongzheng Yang;C. Vild;J. Ju;Xu Zhang;Jianping Liu;Jie Shen;Bin Zhao;W. Lan;F. Gong;Maili Liu;C. Cao;Zhaohui Xu
背景：Vta1和Vps60之间的相互作用刺激Vps4 atp酶，但这种相互作用的结构基础尚不清楚。结果：确定了与Vps60（128 ~ 186）配合物中Vta1 n端结构域（Vta1NTD）的结构。结论：Vps60（128 ~ 186）通过α4′和α5′螺旋与Vta1NTD相互作用，延伸至Vta1NTD MIT2结构域螺旋1 ~ 3。意义：这是一种新颖的MIT识别模式。aaa - atp酶Vps4对多泡体分选途径的功能至关重要，它影响从受体下调到病毒出芽到细胞分裂的细胞现象。Vps4的活性受到Vta1和Vps60相互作用的刺激，但这种相互作用的结构基础尚不清楚。据报道，片段Vps60（128-186）显示出Vps60的全部活性。Vta1通过其n端结构域（Vta1NTD）与Vps60相互作用。在这项工作中，利用核磁共振技术确定了Vps60（128-186）与Vta1NTD配合物的结构，展示了一种新的微管相互作用和运输（MIT）结构域的识别模式，Vps60（128-186）通过螺旋α4 ‘和α5 ’与Vta1NTD相互作用，延伸到Vta1NTD MIT2结构域螺旋1-3。Vps60的结合不会导致Vta1构象的改变，进一步揭示了Vta1和Vps60之间的相互作用以一种意想不到的方式增强了Vps4 atp酶。
Background: Vps4 ATPase is stimulated by the interaction between Vta1 and Vps60, but the structural basis for this interaction remains unclear. Results: The structure of the Vta1 N-terminal domain (Vta1NTD) in complex with Vps60(128–186) was determined. Conclusion: Vps60(128–186) interacts with Vta1NTD through helices α4′ and α5′, extending over Vta1NTD MIT2 domain helices 1–3. Significance: This is a novel MIT recognition mode. The AAA-ATPase Vps4 is critical for function of the multivesicular body sorting pathway, which impacts cellular phenomena ranging from receptor down-regulation to viral budding to cytokinesis. Vps4 activity is stimulated by the interaction between Vta1 and Vps60, but the structural basis for this interaction is unclear. The fragment Vps60(128–186) was reported to display the full activity of Vps60. Vta1 interacts with Vps60 using its N-terminal domain (Vta1NTD). In this work, the structure of Vps60(128–186) in complex with Vta1NTD was determined using NMR techniques, demonstrating a novel recognition mode of the microtubule-interacting and transport (MIT) domain in which Vps60(128–186) interacts with Vta1NTD through helices α4′ and α5′, extending over Vta1NTD MIT2 domain helices 1–3. The Vps60 binding does not result in Vta1 conformational changes, further revealing the fact that Vps4 ATPase is enhanced by the interaction between Vta1 and Vps60 in an unanticipated manner.