A novel extracellular metallopeptidase domain shared by animal host-associated mutualistic and pathogenic microbes.
A novel extracellular metallopeptidase domain shared by animal host-associated mutualistic and pathogenic microbes.
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DOI：
10.1371/journal.pone.0030287
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Hirt RP
中科院分区：
文献类型：
--
作者：
Nakjang S;Ndeh DA;Wipat A;Bolam DN;Hirt RP
粘膜微生物群被认为是我们健康的重要因素，许多疾病状态与正常群落结构的不平衡有关。因此，人们对确定人类与微生物相互作用的分子基础非常感兴趣。在这项工作中，我们研究了微生物在粘膜表面茁壮成长的能力，无论是作为共生菌，共生体还是病原体，使用比较基因组学来识别共同发生的分子特征。我们发现了一个新的结构域，我们将其命名为M60-like/PF13402（新的Pfam入口PF13402），该结构域主要存在于动物宿主粘膜相关的原核和真核微生物的蛋白质中，范围从共生菌到病原体。远亲微生物之间的横向基因转移解释了它们共享的M60-like/PF13402结构域。新结构域的特征是一个类似锌金属肽酶的基序，并且与已知的病毒增强锌金属肽酶有远亲关系。在大多数微生物m60样/PF13402结构域蛋白中检测到信号肽和/或细胞表面锚定特征，表明这些蛋白靶向细胞外底物。这些假定的肽酶的一个重要子集进一步被表征为存在属于碳水化合物结合模块家族5/ 12,32和51的相关结构域以及其他聚糖结合结构域，这表明这些新型蛋白酶针对复杂的糖蛋白，如粘蛋白。一项体外黏液酶试验表明，来自肠道相互作用的拟杆菌（Bacteroides thetaiotaomicron）的含有m60样蛋白/ pf13402蛋白的重组形式可以降解哺乳动物黏液蛋白。本研究揭示m60样结构域是靶向宿主糖蛋白的肽酶。这些肽酶可能在脊椎动物粘膜表面和无脊椎动物消化道中由共生微生物和致病微生物成功定植的过程中发挥重要作用。此外，在MEROPS数据库中描述的各种肽酶家族中的141个条目也被鉴定为碳水化合物结合模块，这为这些聚糖结合域定义了新的功能背景，并为生物医学和工业应用提供了针对特定糖蛋白的蛋白酶设计的机会。
The mucosal microbiota is recognised as an important factor for our health, with many disease states linked to imbalances in the normal community structure. Hence, there is considerable interest in identifying the molecular basis of human-microbe interactions. In this work we investigated the capacity of microbes to thrive on mucosal surfaces, either as mutualists, commensals or pathogens, using comparative genomics to identify co-occurring molecular traits. We identified a novel domain we named M60-like/PF13402 (new Pfam entry PF13402), which was detected mainly among proteins from animal host mucosa-associated prokaryotic and eukaryotic microbes ranging from mutualists to pathogens. Lateral gene transfers between distantly related microbes explained their shared M60-like/PF13402 domain. The novel domain is characterised by a zinc-metallopeptidase-like motif and is distantly related to known viral enhancin zinc-metallopeptidases. Signal peptides and/or cell surface anchoring features were detected in most microbial M60-like/PF13402 domain-containing proteins, indicating that these proteins target an extracellular substrate. A significant subset of these putative peptidases was further characterised by the presence of associated domains belonging to carbohydrate-binding module family 5/12, 32 and 51 and other glycan-binding domains, suggesting that these novel proteases are targeted to complex glycoproteins such as mucins. An in vitro mucinase assay demonstrated degradation of mammalian mucins by a recombinant form of an M60-like/PF13402-containing protein from the gut mutualist Bacteroides thetaiotaomicron. This study reveals that M60-like domains are peptidases targeting host glycoproteins. These peptidases likely play an important role in successful colonisation of both vertebrate mucosal surfaces and the invertebrate digestive tract by both mutualistic and pathogenic microbes. Moreover, 141 entries across various peptidase families described in the MEROPS database were also identified with carbohydrate-binding modules defining a new functional context for these glycan-binding domains and providing opportunities to engineer proteases targeting specific glycoproteins for both biomedical and industrial applications.
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