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补体系统及其糖基化
赵菲1,3 , 党刘毅2, 赵璇3,4, 李可3     
1. Leibniz Institute for Natural Product Research and Infection Biology, Jena 07745, Germany;
2. Department of Molecular Biotechnology, Ghent University, Ghent 9000, Belgium;
3. 西安交通大学第二附属医院,西安 710004;
4. 商洛市中心医院检验科,商洛 726000
摘要: 补体系统是固有免疫系统的重要组成部分,同时也是连接固有免疫和适应性免疫系统的重要桥梁.补体系统由30多种蛋白质组成,且其中绝大多数都经过糖基化修饰.近年来对补体系统的研究,不断揭示出补体系统在抗击病原微生物入侵和维持有机体生理稳态过程中发挥着重要作用.然而补体系统需要严格的调控,不论是激活不足、抑或是过度激活都可能引起疾病的发生.本文概述了近年来对于补体系统的激活、调控和功能研究的最新进展,并首次从糖生物学角度对补体系统蛋白质组分的糖链结构及糖链对相应蛋白质功能的影响进行了综述和小结.
关键词: 补体     糖基化     糖蛋白     调控     H因子    
Complement and Glycosylation
ZHAO Fei1,3, DANG Liu-Yi2, ZHAO Xuan3,4, LI Ke3     
1. Leibniz Institute for Natural Product Research and Infection Biology, Jena 07745, Germany;
2. Department of Molecular Biotechnology, Ghent University, Ghent 9000, Belgium;
3. The Second Affiliated Hospital, School of Medicine, Xi′an Jiaotong University, Xi′an 710004, China;
4. Shangluo Central Hospital, Department of Clinical Laboratory, Shangluo 726000, China
*This work was supported by grants from The Natural Science Foundation of Shaanxi Province(2016YFJZ0020) and The National Natural Science Foundation of China(81470548)
** Corresponding author: Zhao Fei. Tel: 86-29-87678329, E-mail: feizhao821@outlook.com
Li Ke. E-mail: ke.li@mail.xjtu.edu.cn
Received: August 1, 2017 Accepted: September 30, 2017
Abstract: Complement system is an essential part of the innate immunity which serves as a bridge between innate and adaptive immunity. The complement system comprises of over 30 different proteins, most of which are glycoproteins. The recent researches have shown that complement system plays important roles in defense against the evading microbes and maintaining the cellular hemostasis. However, the complement system requires firm controls. Either insufficient activation or over-activation of complement would cause diseases. In this review, we summarize the recent advances in understanding the activation, regulation and the function of complement system and for the first time review the complement system by its glycosylation: we summarize the glycan structures of the complement proteins and analyze the glycosylation impact on the function of the proteins.
Key words: complement     glycosylation     glycoprotein     regulation     factor H    

补体系统是一个高效的识别和效应系统,旨在摧毁入侵的病原微生物并清除受损的宿主细胞.补体系统由30多个不同的血浆蛋白及膜蛋白(包括调节蛋白及受体蛋白)组成,这些补体蛋白大多数是糖基化蛋白,它们共同形成了一个高度调节的蛋白酶级联反应体系.而糖基化是一种重要的蛋白质翻译后修饰,蛋白质糖基化在很多重要的生物学过程(如细胞黏附、分子转运和清除、受体激活、信号转导等)中发挥着关键作用.本文从补体系统的激活、调控和生物学功能三个不同方面对补体系统的最新研究进行了概述,并首次从糖基化的角度对补体系统蛋白质的糖链结构和糖链对蛋白质功能的影响进行了小结.

1 补体系统 1.1 补体系统激活通路

当补体系统被激活时,即产生3种效应功能:a.对靶细胞的调理作用;b.对靶细胞的裂解;c.释放促炎性细胞因子诱导炎症反应的发生.这些效应功能使得补体系统可以识别并清除入侵微生物,清除凋亡或被修饰的自身细胞,并募集免疫细胞到炎症发生部位.补体系统的激活以级联反应方式发生,可以分为4个主要步骤:a.起始阶段;b.C3转化酶激活和扩增;c.C5转化酶激活;d.末端通路激活(图 1).

Fig. 1 Complement activation cascade 图 1 补体系统的激活通路 补体系统的激活包括:a.起始阶段;b. C3转化酶激活和扩增;c. C5转化酶激活;d.末端通路激活4个不同阶段.在起始阶段,三种不同途径可启动补体激活:旁路途径、经典途径及凝集素途径.每个途径均顺序激活并生成C3转化酶,C3转化酶裂解C3生成切割产物C3a和C3b,其中C3b附着于临近表面,可用于:a.表面吞噬调理作用;b.通过旁路途径启动补体级联放大回路;c.结合C3转化酶形成C5转化酶. C5转化酶裂解C5生成C5a和C5b,C5b结合C6、C7、C8、C9形成膜攻击复合物,可在膜表面形成小孔,从而裂解入侵微生物. C3a和C5a是有效的过敏毒素和趋化因子,可促进炎症反应,并募集吞噬细胞到炎症发生位点,促进微生物清除.

1.1.1 起始阶段

补体系统的起始可通过3种不同途径:即旁路途径、经典途径以及凝集素途径(图 1)[1-3].旁路途径通过自发的“tick-over”反应水解C3而激活.C3水解形成活化的C3(H2O),C3(H2O)可结合B因子形成C3(H2O)Bb[4].C3(H2O)Bb对C3具有切割活性,切割C3形成C3a和C3b两种产物,C3b进一步结合B因子则产生旁路途径C3转化酶C3bBb,从而激活旁路途径.由于C3(H2O)不稳定且反应活性较低,在正常生理条件下,C3(H2O)Bb仅持续产生小量的C3b[5-8].经典途径通过C1q的球状头部识别抗原-抗体复合物得到激活.也可通过C1q与C反应蛋白(C-reactive protein,CRP)的结合而得到激活[9].凝集素途径则通过甘露糖结合凝集素(mannan-binding lectin,MBL)或纤维胶凝蛋白(ficolin,FCN)与靶细胞表面的甘露糖(或相关糖)或N-乙酰葡萄糖胺结合而得到激活.经过特异性的识别和结合后,C1q相关丝氨酸蛋白酶C1r和C1s以及甘露糖结合凝集素相关的丝氨酸蛋白酶(MASP1和MASP2) 被激活.激活的C1s和MASP2裂解C4,并产生含有C2结合位点的C4b片段,与C4b结合的C2可进一步被C1r或MASP2切割成C2a和C2b.在此过程中,C2b被释放而C2a仍然结合在C4b上并形成活化的经典/凝集素途径C3转化酶C4bC2a.

1.1.2 C3转化酶阶段

C3转化酶是一种能够快速裂解C3形成调理素C3b和过敏毒素C3a的酶复合物.当C3被裂解,硫酯结构域就在C3b表面暴露出来,使得该蛋白能共价地结合于靶细胞表面.C3b与靶细胞表面的结合可实现三大功能.首先,细胞表面沉积的C3b作为调理素可被补体受体(CR1) 或巨噬细胞表面的补体受体免疫球蛋白超家族(CRIg)结合.C3b与CR1或CRIg的结合促使靶细胞被吞噬或转移.第二,C3b沉积可形成一个平台,促进生成更多的C3转化酶从而持续扩增补体系统的激活.第三,C3b有助于形成C5转化酶并激活下游补体通路.

1.1.3 C5转化酶和末端激活

两种C5转化酶(C3bBbC3b或C4bC2aC3b)均由C3转化酶(C3bBb或C4bC2a)加一个额外的C3b组装生成.C5转化酶裂解C5,释放强效过敏毒素C5a并生成C5b.C5b通过募集C6、C7、C8及C9到靶细胞表面,并插入C9复合物形成小孔(被称为膜攻击复合物)启动末端途径的激活.这些末端补体复合物最终引起靶细胞的裂解[9-10].

1.1.4 过敏毒素C5a和C3a

C5a和C3a是有效的过敏毒素.他们结合多种白细胞如巨噬细胞,中性粒细胞及非免疫细胞表面的相应受体(C5aR/ C3aR).结合后,C5a和C3a激发急性炎症反应,增加血管通透性,增加免疫细胞渗出,推动促炎症介质释放.此外,C5a(C3a也一样,但程度较轻)对巨噬细胞.激活态T细胞和B细胞以及肥大细胞有趋化活性,可募集这些免疫细胞到补体激活的位点.

1.2 补体系统在维持机体稳态和清除病原微生物方面的作用

在生理条件下,C3可自发转化为具有生理活性的C3(H2O),从而持续激活旁路途径[4].生成的C3b或快速在液相由补体H因子和I因子灭活或共价连接到附近的细胞表面[11-13].在完整的宿主细胞表面,沉积的C3b由膜表面调节因子(如CD46、CD55、CR1、C4BP)或液相募集的补体调节因子(如H因子)迅速灭活[14-19],从而使宿主细胞免受补体系统攻击.在凋亡细胞表面,由于补体调节因子的低表达和膜结构的改变,沉积的C3b未完全灭活.因此,旁路途经在凋亡细胞表面的部分激活,从而促进吞噬细胞清除凋亡细胞.此外,经典途径和凝集素途径也在凋亡细胞表面得到激活.经典途径和凝集素途径的起始因子结合于凋亡细胞并与吞噬细胞相互作用,诱发免疫耐受并阻止对自身抗原的免疫反应[10, 20-22].通过这样复杂的补体激活和调控,凋亡细胞在不进一步激活固有和适应性免疫反应的情况下得到清除.而在入侵微生物的表面,补体系统得到完全激活.由旁路途径自发生成的C3b快速在微生物表面沉积,并与B因子和D因子相互作用生成C3转化因子,从而级联放大补体系统的活化[23-24].同时,补体系统释放的过敏毒素(C3a和C5a)募集吞噬细胞到感染病灶处并激活白细胞、内皮细胞及血小板,触发适应性免疫反应.此外,末端途径补体活化产物可形成膜攻击复合物直接裂解入侵的微生物.因此,微生物可迅速被激活的补体系统清除.综上所述,补体系统在自身细胞表面不激活,在凋亡细胞表面部分激活,在入侵微生物表面完全激活,从而在维持机体稳态及清除病原微生物中发挥着重要作用[24].

1.3 补体系统调控

补体系统是一个复杂的固有免疫监督系统,它在维持宿主内稳态和防御微生物中起着至关重要的作用.然而,补体系统需要严格调控.不论是激活不足抑或是过度刺激补体都可能对宿主产生有害影响,引起微生物易感性增加(如脓毒症)或者自身免疫性疾病的发生(如系统性红斑狼疮、风湿性关节炎、阿尔茨海默病、非典型性溶血性尿毒综合症等)[25].此外,补体活化不能区分自身和非自身表面.因此需要调节因子以保护自身组织免受补体系统的攻击.目前,在血浆中,在细胞膜表面均发现了多种可调节补体活化状态、促进自我保护的补体系统调节因子.这些调节因子可在补体激活的各个阶段,同时在液相及宿主细胞表面调控补体激活.然而,迄今为止,仅有2个天然补体系统激活因子被发现.下面,我们将集中介绍几个代表性补体系统调节因子和激活因子.

1.3.1 H因子及H因子相关蛋白家族

H因子是旁路途径的主要血浆调节因子,它的编码区位于常染色体1q32.H因子由20个短串联重复结构域(SCR)组成,主要在肝脏中产生.它是一个巨大的蛋白(155 ku),在血浆循环中的平均浓度为500 mg/L[26-27].作为主要的血浆调节因子,H因子具有多种调节功能,包括:a.促C3b灭活;b.抑制C3转化酶的组装;c.促进C3转化酶加速衰变.研究表明,H因子N端的前4个SCR主要负责这三种调节功能[28-29].此外,H因子还通过结合于宿主细胞协助区分自我和非我表面,形成自我识别.这种自我识别功能主要由H因子C端的SCR 19~20负责:SCR 19~20既可结合于宿主细胞表面的硫酸肝素和糖胺聚糖(GAGs)也可结合于C3b/C3d[30-33].除此之外,SCR 6~7是另一个宿主细胞表面糖胺聚糖的识别区域[34].一旦H因子结合于宿主细胞表面的离子碳水化合物(硫酸肝素或糖胺聚糖)或C3b,H因子就展示出促C3b灭活和促C3转化酶衰变的功能,从而阻断自我细胞表面的C3转化酶激活.

H因子的剪切突变体——H因子样蛋白(factor H like protein 1,FHL-1) 含有H因子的前7个SCRs(SCR1~7) 具备促C3b灭活和促C3转化酶衰变的补体系统调节功能.而且FHL-1也可通过SCR6~7结合于宿主细胞表面的硫酸肝素,从而识别自我表面[35].

H因子相关蛋白(complement factor H related proteins,CFHR)由位于FH基因下游的基因编码,也位于染色体1q32[36].CFHR蛋白的补体调节功能是在近些年中逐步被发现的.CFHR1包含5个SCRs,在人血浆中表现为2种糖基化形式(即包含1条N-糖链的CFHR1α和包含2条N-糖链的CFHR1β)[37].它与H因子竞争结合C3b和硫酸肝素,但缺乏促C3b灭活和促C3转化酶衰变的功能[38-39].在C5转化酶阶段,CFHR1可抑制C5的切割和末端途径C5b-9的形成,因而有效调节C5转化酶的活性.综上所述,CFHR1可抑制H因子在细胞表面的调节活性并抑制C5转化酶活性,目前被归为补体系统调节因子[40].CFHR2有4个SCRs,并且其C端的2个SCRs均可结合C3b.与C3b结合的CFHR2仍允许C3转化酶的形成,但形成的C3转化酶不切割其底物C3,因而CFHR2抑制C3转化酶的激活[41-42].CFHR3和CFHR4可结合C3b和硫酸肝素,显示出增强的促C3b灭活功能[43-45].

1.3.2 备解素(properdin)

备解素是目前最为熟知的补体系统激活因子.不同于大多数其他补体系统调节因子,备解素可由多种细胞生成,如中性粒细胞、单核细胞、T细胞和骨髓祖细胞[46].备解素作为补体系统激活因子,它可以:a.结合C3转化酶,稳定C3转化酶并将其半衰期延长至5~10倍[47];b.结合于多种细胞表面,募集C3b和B因子形成C3转化酶,并作为旁路途径起始的平台[48-49].

1.3.3 CFHR5

CFHR5最近被发现具有补体激活功能[50].CFHR5是H因子相关蛋白中的一个,它包含9个SCRs.CFHR5可在液相中与C3b/C3转化酶相互作用,级联放大C3转化酶.此外,CFHR5可锚定补体激活因子备解素到细胞表面并原位激活补体系统[51].

2 补体系统与糖基化 2.1 蛋白质糖基化

蛋白质糖基化(glycosylation)是指将糖链通过共价方式连接到目标蛋白分子上的过程,是在生物界普遍存在的一种蛋白质翻译后修饰.几乎所有的膜蛋白和分泌蛋白都含有糖基化修饰,只有极少数的蛋白质例外,如小分子的多肽性激素、胰岛素、胰高血糖素等[52-53].蛋白质糖基化在很多重要的生物学过程中发挥着关键作用,包括细胞黏附、分子转运和清除、受体激活、信号转导等[54].

糖蛋白一般含有一个或多个糖链,按照蛋白质上糖链的连接方式,可分为N-,O-及C-糖蛋白[55].一般来讲,N-连接糖基化通常发生于特定的氨基酸位点Asn-X-Ser/Thr (X是指脯氨酸Pro以外的任何氨基酸)中的天冬酰胺上.通常含有1个五糖的核心结构区域,在此基础上可以形成高甘露糖型(high-or oligomannose)、复杂型(complex)和杂合型(hybrid)糖链结构,其末端可以由N-乙酰葡糖胺(GlcNAc)、半乳糖(gal)或唾液酸(sialic acid)等进行修饰[56].常见的O-连接糖链通常可以根据起始的第一个单糖进行分类.比如,黏蛋白型O-糖基化(mucin-type O-glycosylation)由N-乙酰半乳糖胺(GalNAc)起始,其作为第一个单糖连接到丝氨酸或苏氨酸上并且之后可以被拓展为不同类型的糖链结构[57].O-糖链可以包含各种不同核心和末端糖链结构,其末端通常经岩藻糖化和唾液酸化修饰.其他常见类型的O-糖链包括O-甘露糖(O-mannose)、O-岩藻糖(O-fucose)、O-半乳糖(O-galactose)和通常发生在细胞核质中的O-乙酰葡糖胺(O-GlcNAc)糖链等[58].另外,在特定的蛋白上也存在其他的糖基化连接,比如C-甘露糖基化.C-甘露糖基化是由特定的甘露糖转移酶,将α甘露糖通过吲哚C2碳原子连接到Trp-X-X-Trp (X代表任意氨基酸)保守位点的第一个色氨酸上的一种独特的糖基化[59].

2.2 糖基化与疾病

由于蛋白质糖基化修饰的高度复杂性及其在诸多生物学过程中的基础性影响,任何微小的糖基化结构改变都会对细胞的正常生命活动造成深刻的影响[53].目前,多种癌症中都发现了糖基化的改变,包括乳腺癌、肠癌、肝癌、皮肤癌和卵巢癌,癌症相关的糖基化在很多文献中都有详细的阐述[53, 58, 60].同时,越来越多的其他疾病也被发现与糖基化的改变相关,这类疾病通常被称作先天性糖基化缺陷(congenital disorders of glycosylation)[61].先天性糖基化缺陷是一大类由于糖基化修饰的改变导致的遗传学疾病.由于糖链结构的高度不均一性,临床上先天性糖基化缺陷的范围也非常广泛,从几乎正常的表型到非常严重的多器官功能失调,涉及到很多不同的表现形式[62].先天性糖基化缺陷涉及到N-糖基化过程,如甘露糖基转移酶Ⅷ缺陷(CDG-Ig)、甘露糖基转移酶Ⅰ缺陷(CDG-Ik)、甘露糖基转移酶Ⅶ/Ⅸ缺陷(CDG-IL),也有O-糖基化过程,比如O-甘露糖基转移酶1缺陷(Walker-Warburg syndrome)、O-甘露糖基-β1, 2-N-乙酰葡糖胺转移酶1缺陷(muscle-eye-brain disease).当然,先天性糖基化缺陷也会有N-糖基化和O-糖基化同时失调的情况[61, 63].另外,糖基化的改变也可能引起免疫相关的疾病.比如,研究发现白细胞分子黏附缺陷Ⅱ型(LADⅡ),主要表现为反复感染及严重的精神和生长迟滞,即是由于GDP-甘露糖-4, 6-脱氢酶的活性损伤造成的GDP-岩藻糖合成缺陷引起的[64].阵发性夜间血红素尿症(PNH)是由于粒细胞和B淋巴细胞上的GDP锚的生物合成缺陷引起的,其表现为反复发作的血管内溶血[65].需要注意的是,糖基化相关的疾病不仅涉及到糖基转移酶和糖基化酶的改变,偶然发生的某些蛋白的糖基化改变也可能导致糖基化疾病的发生,最近在对一个人类疾病数据库中糖蛋白突变的分析表明,糖基化发生改变的蛋白质中氨基酸突变的概率比随机突变概率要更高一些[54].然而,目前尚没有对于由补体系统糖基化改变而引起的疾病的研究.

2.3 补体蛋白的糖基化

补体系统糖蛋白一般是在肝脏细胞、巨噬细胞或淋巴组织中合成的.它们可能包含由1~8个不同的N-糖基化位点(图 2):例如,C1q单体只有一个N-糖基化位点,而C2及H因子都包含8个N-糖基化位点.另一些补体蛋白,如在宿主细胞表面的DAF和CD59则包含O-糖链.大多数在肝脏中合成的补体蛋白(如C1r、C1s、C2、C3、C4、C5、C6、C8、C9、B因子、I因子及C4BP)都含有复杂型双天线糖链并伴有不同程度的唾液酸化.其中C3仅含有高甘露糖型糖链[66].有些补体蛋白包含低丰度的核心岩藻糖,例如,与C1s蛋白相连的糖链中仅有17%的糖链含有核心岩藻糖.与其他在肝脏中合成的补体蛋白相比,C4BP(A链)及三聚C8的α链和β链唾液酸化程度都较低,这表明在这两种蛋白质中,唾液酸转移酶与糖基化位点的接触更少更难.在淋巴组织中合成的补体蛋白包括C1q、备解素及C7.与肝脏中合成的补体蛋白相似,这些由淋巴组织合成的补体蛋白也包含复杂型双天线糖链.不同的是,这些淋巴组织合成的蛋白(C1q、备解素及C7) 无不是核心岩藻糖化的,不像肝脏中合成的补体蛋白核心岩藻糖化程度较低.

Fig. 2 Domain organization of proteins in the complement cascade and their potential glycosylation sites 图 2 补体通路蛋白质结构域及其潜在糖基化位点示意图
2.4 糖基化对补体蛋白功能的影响

补体系统由30多个不同的血浆蛋白及膜蛋白构成,这些蛋白大部分都是糖基化蛋白.然而,对于蛋白质糖基化在补体系统激活及调控中作用的研究是有限的.在此,我们对H因子、B因子及I因子的糖链对其功能的影响做一小结.

2.4.1 糖链参与调节B因子和C3b的相互作用

B因子是一个球状蛋白,包含Ba和Bb两个部分(图 2).Ba片段包括3个短串联重复结构域(SCR1~3),Bb片段包括1个vWF-A结构域,和1个丝氨酸蛋白酶(SP)结构域(图 2).当结合C3b之后,B因子经过一系列构象变化并呈现出V形结构,其中Ba部分在打开的位置[67].B因子上有4个潜在N-糖基化位点,这4个位点均包含唾液酸化的复杂型双天线糖链.其中糖基化位点N260位于与C3b相互作用位点附近,同时靠近Mg2+结合裂[68].对于N260和D254的双突变研究表明,当除去N260上的寡糖链后,B因子对C3b的结合活性增强[69].该结果显示N-糖链可能参与调控B因子对C3b的结合.此外,另一个B因子的N-糖基化位点N353靠近D因子对B因子的切割位点,有可能对D因子的切割作用产生一定的空间位阻从而下调该切割过程,从而抑制补体系统激活.

2.4.2 糖链与H因子对自身细胞识别

H因子是一个N-糖基化蛋白,包含复杂型、双天线双唾液酸化、非岩藻糖基化糖链[70].H因子可通过与宿主细胞表面的唾液酸/糖胺聚糖的离子相互作用从而区分宿主细胞以及病原微生物[71-73].非激活的自身结构(宿主细胞)已被证明富含唾液酸/糖胺聚糖,如硫酸肝素.这些阴离子结构(唾液酸/糖胺聚糖)被认为提高了H因子对细胞表面沉积的C3b的亲和性,从而增加了H因子对自身细胞的结合并对自身细胞表面的补体激活产生调控.然而,H因子上的糖链对于该离子识别过程的功能性影响仍是未知的.

一项研究分别比较了野生型H因子和去糖基化H因子在兔红细胞和羊红细胞表面对C3转化酶衰变的影响.实验结果表明,去糖基化H因子对C3转化酶的衰变有更强的促进功能,该结果在兔/羊红细胞上均得到证实[74].然而,从未有人直接验证过野生型/去糖基化H因子对硫酸肝素的直接结合效力有没有差异.此外,结构分析表明,糖基化对于H因子的折叠和正确构象的形成不是必需的[75].综上所述,H因子上的糖链结构对H因子生物学功能的影响仍是一个有趣的、尚待发掘的问题.

2.4.3 糖链与I因子的切割活性

I因子是一种具有高度底物特异性的酶,它可以在特定辅助因子(C4BP、H因子、CD46、CR1) 的作用下切割C4b或C3b形成无活性的切割产物[76-77].I因子以重度N-糖基化的异二聚体形式在人血浆中循环,其两条单链由二硫键相连,每条单链分别包含3个N-寡糖侧链(图 2).I因子主要包含复杂型双天线糖链,其中46%是双唾液酸化的,26%是单唾液酸化的糖链[78].由于I因子与H因子及C3b的相互作用主要是离子性的,I因子上具有的带负电荷的糖链可能影响它与辅助因子的相互作用[79],例如:Ullman等[80]的研究表明,含有中性寡聚岩藻糖链的重组I因子与纯化的天然人源I因子相比,只有55%的切割活性.然而,另一项研究表明,天然的I因子和去糖基化I因子,有着相似的水解C3(NH3) 的功能[80-81].因此,糖链对于I因子的生物学功能有何影响仍然需要进一步探究.

除以上三种补体蛋白外,有研究表明,小鼠C4蛋白糖基化缺失会导致其血清的溶血活性下降[82],而CD59上的糖链可能影响CD59在细胞膜上的极化并保护CD59免受蛋白酶分解[83],MCP,即CD46可保护细胞免受补体介导的细胞溶解,其结构域CCP-2、CCP-4上的糖基化修饰对于该保护功能是必需的,其STP结构域上的O-糖基化对该过程稍有影响,而CCP-1上的糖基化是无影响的[84].以上研究进一步表明糖基化修饰对于补体系统蛋白质功能可能有着深刻影响,但目前我们对于补体系统糖基化和其功能的了解仍处于起步阶段,还有非常广阔的空间有待探索.

3 小结和展望

补体系统是固有免疫系统的重要组成部分,此外补体蛋白还可通过与多个免疫细胞的通讯来协调免疫反应,因而补体系统是连接固有免疫和适应性免疫系统的重要桥梁.补体系统在清除病原微生物、维持机体稳态等方面有着重要作用.然而补体系统需要严格调控,补体系统失调有可能引起感染性或是自身免疫性疾病的发生.补体系统由30多种蛋白组成,且其中绝大多数是糖基化蛋白.糖基化是一种重要且广泛存在的蛋白质翻译后修饰,糖基化对于蛋白质折叠、构象形成、稳定性等方面有着重要的影响.补体系统组分的糖基化及其对相应蛋白质功能的影响在近些年来得到了越来越多的重视.本文从补体系统的激活、调控及功能方面对补体系统研究的新进展进行了概述,并首次从糖基化角度描述了补体系统蛋白及糖链对补体系统蛋白质功能的影响.虽然目前对于补体蛋白糖基化的研究仍处于起步阶段,但是现有的研究已经显示出糖链结构对于补体系统蛋白质功能有着不可忽视的影响,暗示着这一领域的广阔发展前景.

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中国科学院生物物理研究所和中国生物物理学会共同主办
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文章信息

赵菲, 党刘毅, 赵璇, 李可
ZHAO Fei, DANG Liu-Yi, ZHAO Xuan, LI Ke
补体系统及其糖基化
Complement and Glycosylation
生物化学与生物物理进展, 2017, 44(10): 888-897
Progress in Biochemistry and Biophysics, 2017, 44(10): 888-897
http://dx.doi.org/10.16476/j.pibb.2017.0320

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收稿日期: 2017-08-01
接受日期: 2017-09-30

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