Homo-oligomerization facilitates the interferon-antagonist activity of the ebolavirus VP35 protein
Homo-oligomerization facilitates the interferon-antagonist activity of the ebolavirus VP35 protein
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DOI：
10.1016/j.virol.2005.06.044
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发表时间：
2005-10-25
期刊：
影响因子：
3.7
通讯作者：
Basler, CF
中科院分区：
文献类型：
--
作者：
St Reid, P;Cárdenas, WB;Basler, CF
我们已经确定了一个假定的卷曲螺旋基序内的埃博拉病毒VP 35蛋白的氨基末端的一半。交联研究证明了VP 35形成三聚体的能力，这与功能性卷曲螺旋基序的存在一致。如通过免疫共沉淀研究推断的，缺乏卷曲螺旋基序或具有设计为破坏卷曲螺旋功能的突变的VP 35突变体在寡聚化中是有缺陷的。VP 35抑制激活干扰素调节因子3（IRF-3）的信号传导并抑制（IFN）-α/β产生。比较VP 35突变体阻断IFN应答的能力的实验表明，保留假定的卷曲螺旋基序的VP 35氨基末端不能抑制IFN应答，而VP 35羧基末端弱抑制IFN应答的活化。当异源三聚化基序融合到VP 35的羧基末端一半时，IFN-拮抗剂功能恢复，表明氨基末端的寡聚化功能促进了由VP 35的羧基末端一半发挥的“IFN-拮抗剂”功能。(c)2005年爱思唯尔公司All rights reserved.
We have identified a putative coiled-coil motif within the amino-terminal half of the ebolavirus VP35 protein. Cross-linking studies demonstrated the ability of VP35 to form trimers, consistent with the presence of a functional coiled-coil motif. VP35 mutants lacking the coiled-coil motif or possessing a mutation designed to disrupt coiled-coil function were defective in oligomerization, as deduced by co-immunoprecipitation studies. VP35 inhibits signaling that activates interferon regulatory factor 3 (IRF-3) and inhibits (IFN)-alpha/beta production. Experiments comparing the ability of VP35 mutants to block IFN responses demonstrated that the VP35 amino-terminus, which retains the putative coiled-coil motif, was unable to inhibit IFN responses, whereas the VP35 carboxy-terminus weakly inhibited the activation of IFN responses. IFN-antagonist function was restored when a heterologous trimerization motif was fused to the carboxy-terminal half of VP35, suggesting that an oligomerization function at the amino-terminus facilitates an "IFN-antagonist" function exerted by the carboxy-terminal half of VP35. (c) 2005 Elsevier Inc. All rights reserved.