來自中科院生物物理研究所,，美國辛辛那提兒童病醫(yī)院醫(yī)學(xué)中心的研究人員發(fā)表了題為“Crystallography of a Lewis-Binding Norovirus, Elucidation of Strain-Specificity to the Polymorphic Human Histo-Blood Group Antigens”的文章，闡述和探討了諾羅病毒與Lewis型人類組織血型抗原受體（HBGAs）結(jié)合特異性的結(jié)構(gòu)基礎(chǔ)與分子機制,。這一研究成公布在美國《PLoS病原體》（PLoS Pathogens）期刊上。
這項研究由生物物理研究所饒子和院士研究組的李雪梅研究員與美國辛辛那提兒童病醫(yī)院醫(yī)學(xué)中心Xi Jiang教授研究組的共同研究完成,，得到了國家“863”計劃、國家自然科學(xué)基金和重大疾病專項基金的資助,。
諾羅病毒（Norovirus）是引起人類傳染性胃腸炎的主要非細菌性病原體,。不同種株的諾羅病毒識別人體消化道粘膜上皮細胞表面的不同類型的組織-血型抗原，識別過程通過諾羅病毒衣殼蛋白的P結(jié)構(gòu)域與HBGAs末端的寡糖殘基結(jié)合來完成,。
VA207作為G-II基因群的病毒株,，主要識別lewis型血糖抗原，這與目前已具有結(jié)構(gòu)基礎(chǔ)的VA387,、諾瓦克病毒（Norwalk Virus）有著不同的結(jié)合模式,。
在這篇文章中,，研究人員根據(jù)諾羅病毒VA207衣殼蛋白P結(jié)構(gòu)域與Lewis四糖的復(fù)合物晶體結(jié)構(gòu)發(fā)現(xiàn),，識別四糖的活性位點位于蛋白二聚體作用界面的口袋中，蛋白和四糖分子之間具有穩(wěn)定而廣泛的氫鍵網(wǎng)絡(luò)體系,，參與蛋白-寡糖相互作用的殘基在諾羅病毒家族中具有較高的同源性,，且作用模式屬于典型的諾羅病毒G-II型基因族的作用模式。突變實驗和蛋白-寡糖作用檢測實驗結(jié)果證實,，參與該作用的氨基酸殘基對于病毒與宿主的相互識別作用具有重要意義,，對該殘基的突變將導(dǎo)致與原來HBGAs寡糖分子結(jié)合能力的喪失并使其具有識別新的HBGAs寡糖分子的能力。
這項研究通過對諾羅病毒衣殼蛋白與lewis寡糖復(fù)合物的結(jié)構(gòu)和功能研究,，有助于對諾羅病毒與HBGAs的識別作用和侵染宿主提供全面,、合理的結(jié)構(gòu)解釋，同時為研發(fā)抗諾羅病毒藥物提供重要的科學(xué)依據(jù),。（生物谷 Bioon.com）
doi:10.1371/journal.ppat.1002152
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Crystallography of a Lewis-Binding Norovirus, Elucidation of Strain-Specificity to the Polymorphic Human Histo-Blood Group Antigens
Yutao Chen, Ming Tan, Ming Xia, Ning Hao, Xuejun C. Zhang, Pengwei Huang, Xi Jiang, Xuemei Li, Zihe Rao
Noroviruses, an important cause of acute gastroenteritis in humans, recognize the histo-blood group antigens (HBGAs) as host susceptible factors in a strain-specific manner. The crystal structures of the HBGA-binding interfaces of two A/B/H-binding noroviruses, the prototype Norwalk virus (GI.1) and a predominant GII.4 strain (VA387), have been elucidated. In this study we determined the crystal structures of the P domain protein of the first Lewis-binding norovirus (VA207, GII.9) that has a distinct binding property from those of Norwalk virus and VA387. Co-crystallization of the VA207 P dimer with Ley or sialyl Lex tetrasaccharides showed that VA207 interacts with these antigens through a common site found on the VA387 P protein which is highly conserved among most GII noroviruses. However, the HBGA-binding site of VA207 targeted at the Lewis antigens through the α-1, 3 fucose (the Lewis epitope) as major and the β-N-acetyl glucosamine of the precursor as minor interacting sites. This completely differs from the binding mode of VA387 and Norwalk virus that target at the secretor epitopes. Binding pocket of VA207 is formed by seven amino acids, of which five residues build up the core structure that is essential for the basic binding function, while the other two are involved in strain-specificity. Our results elucidate for the first time the genetic and structural basis of strain-specificity by a direct comparison of two genetically related noroviruses in their interaction with different HBGAs. The results provide insight into the complex interaction between the diverse noroviruses and the polymorphic HBGAs and highlight the role of human HBGA as a critical factor in norovirus evolution.
