近日,，國際著名雜志Nature Communications刊登了中科院微生物研究所高福研究員等的研究成果“Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesio。”，文章中,，作者解析了gD與其細(xì)胞受體nectin-1的復(fù)合體結(jié)構(gòu), 揭示了gD與nectin-1在分子水平上的相互作用模式。
有囊膜病毒的囊膜與宿主細(xì)胞膜融合是病毒侵入宿主最關(guān)鍵的步驟之一,，根據(jù)膜融合的特點(diǎn)不同,，可將囊膜病毒分為I型（流感病毒、艾滋病毒）,，II型（日本腦炎病毒,、西尼羅河病毒）和III型（皰疹病毒）。I型和II型囊膜病毒由于只需要單一糖蛋白來完成融合,，過程相對簡單,，因而已經(jīng)有較深入的研究。但是III型囊膜病毒的膜融合需要多個病毒蛋白與多個細(xì)胞表面受體參與，相互協(xié)調(diào)才能完成膜融合,，整個過程比較復(fù)雜,，其機(jī)制還很不清楚。單純皰疹病毒作為III型囊膜病毒的典型代表,，研究清楚其囊膜蛋白與受體相互作用方式,，對闡明這類III型囊膜病毒的侵入機(jī)制有重要意義，同時,，也會為開發(fā)抑制皰疹病毒融合的小分子藥物奠定理論基礎(chǔ),。
單純皰疹病囊膜表面糖蛋白D（gD）在膜融合過程中發(fā)揮著啟動膜融合進(jìn)程的重要作用，這需要通過結(jié)合受體來實(shí)現(xiàn),。Nectin-1是重要的細(xì)胞表面粘附分子,，也是gD的關(guān)鍵性受體。盡管Nectin-1作為gD的受體早已知曉,，多年來人們對二者的相互作用方式也有種種猜測,，但一直都沒有確定的結(jié)論。最近,，中科院微生物研究所高福研究員課題組通過結(jié)構(gòu)生物學(xué)技術(shù),，解析了gD與其細(xì)胞受體nectin-1的復(fù)合體結(jié)構(gòu), 揭示了gD與nectin-1在分子水平上的相互作用模式。研究表明,，gD蛋白結(jié)合于nectin-1分子二聚化的接觸面上,，這一結(jié)合模式破壞了nectin-1自身的二聚化，進(jìn)而削弱了細(xì)胞粘附,，有利于病毒入侵,。這種作用模式暴露了HSV病毒“剝削”宿主分子為己用的機(jī)制。（生物谷Bioon.com）
doi:10.1038/ncomms1571
PMC:
PMID:
Binding of herpes simplex virus glycoprotein D to nectin-1 exploits host cell adhesion
Na Zhang,1, 2, 7 Jinghua Yan,1, 7 Guangwen Lu,1, 7 Zhengfei Guo,1, 3 Zheng Fan,4 Jiawei Wang,5 Yi Shi,1 Jianxun Qi1 & George F Gao1, 2, 6
Multiple surface envelope proteins are involved in the human herpes simplex virus type 1 entry and fusion. Among them, glycoprotein D (gD) has an important role by binding to the host receptors such as herpes virus entry mediator and nectin-1. Although the complex structure of gD with herpes virus entry mediator has been established, the binding mode of gD with the nectin-1 is elusive. Nectin-1 is a member of the immunoglobulin (Ig)-like (three Ig-like domains) cell adhesion molecules and is believed to form a homodimer to exert its functions. Here we report the complex structure of gD and nectin-1 (three Ig domains), revealing that gD binds the first Ig domain of nectin-1 in a similar mode to the nectin-1 homodimer interaction. The key amino acids responsible for nectin-1 dimerization are also used for gD/nectin-1 binding. This result indicates that binding of gD to nectin-1 would preclude the nectin-1 dimerization, consequently abolishing its cell adhesion function.
