摘要
HIV-1 基质蛋白P17在病毒生命周期中起着重要作用。它是从HIV-1感染细胞的外空间释放并在患者组织中积累,甚至对那些利用高活性抗逆转录病毒疗法成功治疗的患者也是如此。细胞外P17抑制许多直接或间接与艾滋病相关的细胞生物学功能。所有P17活动都取决于位于蛋白质N端的功能表位和表达于靶细胞上的不同受体之间的相互作用。这些发现表明了阻碍p17和p17受体之间的相互作用对阻断AIDS的重要性。本文讨论了P17与硫酸乙酰肝素蛋白多糖(HSPGs),以及与趋化因子(CXC)受体1(CXCR1)和受体2(CXCR2)之间的相互作用。我们对P17如何与其受体相互作用、这些相互作用如何成为P17生物活性中心进行了阐述。此外,我们发现了P17变种的存在、并命名为s75x,与P17相比,s75x对B细胞增殖有着相反的作用。P17与G蛋白偶联受体相互作用的二位点模型为自然发生在原发性氨基酸结构中的突变为什么能促使s75x激活Akt信号通路、促进B细胞生长和转化提供了合理的解释。P17与HSPGs、CXCR1和CXCR2细胞相互作用的识别将有助于寻找阻断所有p17和p17相互作用以及p17有害影响的治疗方法。
关键词: HIV-1,基质蛋白p17,CXCR1、CXCR2,硫酸乙酰肝素蛋白多糖,信号通路,治疗疫苗,CXCR1单倍型
图形摘要
Current Drug Targets
Title:HIV-1 Matrix Protein p17 and its Receptors
Volume: 17 Issue: 1
Author(s): Francesca Caccuri, Stefania Marsico, Simona Fiorentini, Arnaldo Caruso and Cinzia Giagulli
Affiliation:
关键词: HIV-1,基质蛋白p17,CXCR1、CXCR2,硫酸乙酰肝素蛋白多糖,信号通路,治疗疫苗,CXCR1单倍型
摘要: The HIV-1 matrix protein p17 (p17) plays a crucial role in the virus life cycle. It is released in the extracellular space from HIV-1-infected cells and accumulates in the tissues of patients, even in those successfully treated with highly active antiretroviral therapy. Extracellular p17 deregulates the biological functions of many different cells that are directly or indirectly implicated in AIDS pathogenesis. All p17 actions depend on interaction between its functional epitope (AT20), located at the protein N-terminal region, and different receptors expressed on target cells. This finding corroborates the importance of impeding p17/p17 receptors interaction as a contribution to block AIDS. In this article we review the interaction of p17 with heparan sulfate proteoglycans (HSPGs) and with the chemokine (C-X-C motif) receptor 1 (CXCR1) and 2 (CXCR2). We provide details on how p17 interacts with its receptors and how these interactions are central to the p17 biological activities. Moreover, we highlight the existence of a p17 variant, named S75X, which displays opposite effects on B-cell proliferation as compared to p17. A two-site model for p17 interaction with G-coupled receptors provides a possible explanation on how mutations naturally occurring within the primary amino acid structure can lead S75X to activate the Akt signaling pathway and to promote B-cell growth and transformation. Identification of p17 interaction with HSPGs, CXCR1 and CXCR2 as a fundamental event in supporting its activity could help to find new treatment approaches aimed at blocking all p17/p17 receptors interactions and, consequently, p17 detrimental activities.
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Cite this article as:
Francesca Caccuri, Stefania Marsico, Simona Fiorentini, Arnaldo Caruso and Cinzia Giagulli , HIV-1 Matrix Protein p17 and its Receptors, Current Drug Targets 2016; 17 (1) . https://dx.doi.org/10.2174/1389450116666150825110840
DOI https://dx.doi.org/10.2174/1389450116666150825110840 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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