细胞CD200蛋白的病毒同源物的结构特性：卡波西肉瘤相关疱疹病毒vOX2

Structural properties of a viral orthologue of cellular CD200 protein: KSHV vOX2.

作者信息

Amini Abbas Ali, Solovyova Alexandra S, Sadeghian Hamid, Blackbourn David J, Rezaee S A Rahim

机构信息

Inflammation and Inflammatory Diseases Research Centre, Medical school, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.

Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Catherine Cookson Building, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.

出版信息

Virology. 2015 Jan 1;474:94-104. doi: 10.1016/j.virol.2014.10.020. Epub 2014 Nov 14.

DOI:10.1016/j.virol.2014.10.020

PMID:25463607

Abstract

Kaposi׳s sarcoma-associated herpesvirus (KSHV) vOX2 is a cell surface glycoprotein expressed during viral lytic replication to suppress host inflammatory reactions. Here we have characterised vOX2 with biochemical, biophysical and bioinformatics tools and as a result propose a 3-dimensional model for vOX2 based on structural and functional homology with the PD-L1 protein. To validate this model, vOX2 was characterised by analytical ultracentrifugation (AUC) and circular dichroism spectroscopy (CD). The results identified the potential glycosylation sites and revealed that vOX2 is predominantly a beta-folded molecule with an RGD adhesion motif exposed on the C-terminal domain. The protein exists in monomer-dimer equilibrium similar to its IgV-type folded homologues, with 30-36% glycosylation and the molecular weight of the extracellular fragment of molecule is 32.0-33.6 kDa, much less than 50 kDa. Thus, the structural similarity to PD-L1 verifies its immunomodulatory potential and the RGD motif suggests an adhesive capacity.

摘要

卡波西肉瘤相关疱疹病毒（KSHV）的vOX2是一种在病毒裂解复制过程中表达的细胞表面糖蛋白，用于抑制宿主炎症反应。在此，我们运用生化、生物物理和生物信息学工具对vOX2进行了表征，并基于与PD-L1蛋白的结构和功能同源性，提出了vOX2的三维模型。为验证该模型，我们通过分析型超速离心（AUC）和圆二色光谱（CD）对vOX2进行了表征。结果确定了潜在的糖基化位点，并揭示vOX2主要是一种β折叠分子，其RGD黏附基序暴露于C末端结构域。该蛋白与其IgV型折叠同源物类似，以单体-二聚体平衡形式存在，糖基化程度为30%-36%，分子细胞外片段的分子量为32.0-33.6 kDa，远小于50 kDa。因此，与PD-L1的结构相似性证实了其免疫调节潜力，而RGD基序则表明其具有黏附能力。