Role for the conserved N-terminal cysteines in the anti-chemokine activities by the chemokine-like protein MC148R1 encoded by Molluscum contagiosum virus
Role for the conserved N-terminal cysteines in the anti-chemokine activities by the chemokine-like protein MC148R1 encoded by Molluscum contagiosum virus
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保守的 N 端半胱氨酸在传染性软疣病毒编码的趋化因子样蛋白 MC148R1 的抗趋化因子活性中的作用
DOI：
10.1016/j.virol.2011.07.001
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发表时间：
2011-09-01
期刊：
影响因子：
3.7
通讯作者：
Alkhatib, Ghalib
中科院分区：
文献类型：
--
作者：
Jin, Qingwen;Altenburg, Jeffrey D.;Alkhatib, Ghalib
传染性软疣痘病毒（MCV）1型和2型编码两种趋化因子样蛋白MC 148 R1和MC 148 R2。据信，MC 148 R蛋白通过阻断炎症反应而起作用。然而，MC 148 R蛋白的生物活性机制和其他趋化因子中不存在的额外C-末端半胱氨酸的作用尚不清楚。在这里，我们在两种不同的测定系统中证明了His标记的MC 148 R1取代了CXCL 12 α和CXCR 4之间的相互作用。N-末端半胱氨酸而不是额外的C-末端半胱氨酸调节这种置换。His-标记的MC 148 R1阻断了CXCL 12 α和CXCL 12 β。介导的趋化性和MIP-1 α介导的趋化性。相反，MC 148 R2阻断MIP-1 α介导的趋化性，但不阻断CXCL 12 α介导的趋化性。通过针对MC 148 R1或CXCL 12 α的抗体进行免疫沉淀，然后通过针对其他蛋白质的抗体进行免疫印迹和检测，证明了His标记的CXCL 12 α和His标记的MC 148 R1的物理相互作用。与趋化因子的相互作用可能掩盖受体相互作用位点，导致结合减少和生物活性受损。(C)2011 Elsevier Inc. All rights reserved.
Molluscum contagiosum poxvirus (MCV) type 1 and type 2 encode two chemokine-like proteins MC148R1 and MC148R2. It is believed that MC148R proteins function by blocking the inflammatory response. However, the mechanism of the proposed biological activities of MC148R proteins and the role of the additional C-terminal cysteines that do not exist in other chemokines are not understood. Here, we demonstrated in two different assay systems that His-tagged MC148R1 displaces the interaction between CXCL12 alpha and CXCR4. The N-terminal cysteines but not the additional C-terminal cysteines modulate this displacement. His-tagged MC148R1 blocked both CXCL12 alpha.-mediated and MIP-1 alpha-mediated chemotaxis. In contrast, MC148R2 blocked MIP-1 alpha-mediated but not CXCL12 alpha-mediated chemotaxis. Immunoprecipitation by antibodies to MC148R1 or CXCL12 alpha followed by immunoblotting and detection by antibodies to the other protein demonstrated physical interaction of His-tagged CXCL12 alpha and His-tagged MC148R1. Interaction with chemokines might mask the receptor interaction site resulting in decreased binding and impairment of the biological activities. (C) 2011 Elsevier Inc. All rights reserved.