Sulfated glycan recognition by carbohydrate sulfatases of the human gut microbiota.

Sulfated glycans are ubiquitous nutrient sources for microbial communities that have co-evolved with eukaryotic hosts. Bacteria metabolise sulfated glycans by deploying carbohydrate sulfatases that remove sulfate esters. Despite the biological importance of sulfatases, the mechanisms underlying their ability to recognise their glycan substrate remain poorly understood. Here, we utilise structural biology to determine how sulfatases from the human gut microbiota recognise sulfated glycans. We reveal 7 new carbohydrate sulfatase structures span four S1 sulfatase subfamilies. Structures of S1_16 and S1_46 represent the first structures of these subfamilies. Structures of S1_11 and S1_15 demonstrate how non-conserved regions of the protein drive specificity towards related but distinct glycan targets. Collectively, these data reveal that carbohydrate sulfatases are highly selective for the glycan component of their substrate. These data provide new approaches for probing sulfated glycan metabolism, whilst revealing the roles carbohydrate sulfatases play in host-glycan catabolism.

硫酸化聚糖是与真核宿主共同进化的微生物群落无处不在的营养来源。细菌通过部署能够去除硫酸酯的碳水化合物硫酸酯酶来代谢硫酸化聚糖。尽管硫酸酯酶在生物学上很重要，但其识别聚糖底物能力的潜在机制仍知之甚少。在此，我们利用结构生物学来确定人类肠道微生物群的硫酸酯酶如何识别硫酸化聚糖。我们揭示了7种新的碳水化合物硫酸酯酶结构，涵盖4个S1硫酸酯酶亚家族。S1_16和S1_46的结构代表了这些亚家族的首批结构。S1_11和S1_15的结构展示了蛋白质的非保守区域如何驱动对相关但不同的聚糖靶点的特异性。总体而言，这些数据表明碳水化合物硫酸酯酶对其底物的聚糖成分具有高度选择性。这些数据为探究硫酸化聚糖代谢提供了新方法，同时揭示了碳水化合物硫酸酯酶在宿主 - 聚糖分解代谢中所起的作用。