Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides.,Nature Communications

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Structural basis of mammalian high-mannose N-glycan processing by human gut Bacteroides.
Nature Communications ( IF 14.7 ) Pub Date : 2020-02-14 , DOI: 10.1038/s41467-020-14754-7
Beatriz Trastoy ₁ , Jonathan J Du _{2,

3} , Erik H Klontz _{2,

4,

5} , Chao Li ₆ , Javier O Cifuente ₁ , Lai-Xi Wang ₆ , Eric J Sundberg _{2,

3,

4,

7} , Marcelo E Guerin _{1,

8}

Affiliation

The human gut microbiota plays a central role not only in regulating the metabolism of nutrients but also promoting immune homeostasis, immune responses and protection against pathogen colonization. The genome of the Gram-negative symbiont Bacteroides thetaiotaomicron, a dominant member of the human intestinal microbiota, encodes polysaccharide utilization loci PULs, the apparatus required to orchestrate the degradation of a specific glycan. EndoBT-3987 is a key endo-β-N-acetylglucosaminidase (ENGase) that initiates the degradation/processing of mammalian high-mannose-type (HM-type) N-glycans in the intestine. Here, we provide structural snapshots of EndoBT-3987, including the unliganded form, the EndoBT-3987-Man9GlcNAc2Asn substrate complex, and two EndoBT-3987-Man9GlcNAc and EndoBT-3987-Man5GlcNAc product complexes. In combination with alanine scanning mutagenesis and activity measurements we unveil the molecular mechanism of HM-type recognition and specificity for EndoBT-3987 and an important group of the GH18 ENGases, including EndoH, an enzyme extensively used in biotechnology, and for which the mechanism of substrate recognition was largely unknown.

中文翻译：

人类肠道拟杆菌加工哺乳动物高甘露糖 N-聚糖的结构基础。

人类肠道微生物群不仅在调节营养物质代谢方面发挥着核心作用，而且在促进免疫稳态、免疫反应和防止病原体定植方面发挥着核心作用。革兰氏阴性共生体 Bacteroides thetaiotaomicron 是人类肠道微生物群的主要成员，其基因组编码多糖利用位点 PUL，这是协调特定聚糖降解所需的装置。 EndoBT-3987 是一种关键的内切-β-N-乙酰氨基葡萄糖苷酶 (ENGase)，可启动哺乳动物高甘露糖型（HM 型）N-聚糖在肠道中的降解/加工。在这里，我们提供了 EndoBT-3987 的结构快照，包括未配体形式、EndoBT-3987-Man9GlcNAc2Asn 底物复合物以及两个 EndoBT-3987-Man9GlcNAc 和 EndoBT-3987-Man5GlcNAc 产物复合物。结合丙氨酸扫描诱变和活性测量，我们揭示了 EndoBT-3987 和一组重要的 GH18 ENGase 的 HM 型识别和特异性的分子机制，包括 EndoH，一种广泛用于生物技术的酶，其机制底物识别很大程度上是未知的。

更新日期：2020-02-14

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