Wang Tongtong, Huang Wenze, Xu Kui, Sun Yitong, Zhang Qiangfeng Cliff, Yan Chuangye, Li Zhangqiang, Yan Nieng
Beijing Frontier Research Center for Biological Structures, State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Institute of Bio-Architecture and Bio-Interactions, Shenzhen Medical Academy of Research and Translation, Shenzhen 518107, Guangdong, China.
Proc Natl Acad Sci U S A. 2025 Jan 7;122(1):e2423943122. doi: 10.1073/pnas.2423943122. Epub 2024 Dec 31.
Despite the recent breakthrough in structure determination and prediction of proteins, the structural investigation of carbohydrates remains a challenge. Here, we report the cryo-EM analysis of a glycofibril found in the freshwater in the Tsinghua Lotus Pond. The fibril, which we name TLP-4, is made of a linear chain of tetrapeptide repeats coated with >4 nm thick glycans. In each repeat, two glycans are O-linked to a 3,4-dihydroxyproline and another glycan attaches to the adjacent Ser or Thr. The fibril structure is entirely maintained through glycan packing. Bioinformatic analysis confirms the conservation of the TLP-4 repeats across species, suggesting the existence of a large number of glycofibrils to be discovered. Our findings not only provide valuable insights into the structural roles of glycans in bio-assemblies but also demonstrate the potential of our recently formulated research strategy of CryoSeek to find bioentities and establish prototypes for structural studies of carbohydrates.
尽管近期在蛋白质结构测定和预测方面取得了突破，但碳水化合物的结构研究仍然是一项挑战。在此，我们报告了对在清华荷塘淡水中发现的一种糖原纤维的冷冻电镜分析。这种纤维，我们命名为TLP-4，由四肽重复序列的线性链组成，表面覆盖着厚度超过4纳米的聚糖。在每个重复序列中，两个聚糖通过O-连接与一个3,4-二羟基脯氨酸相连，另一个聚糖则连接到相邻的丝氨酸或苏氨酸上。纤维结构完全通过聚糖堆积得以维持。生物信息学分析证实了TLP-4重复序列在物种间的保守性，这表明还有大量的糖原纤维有待发现。我们的研究结果不仅为聚糖在生物组装中的结构作用提供了有价值的见解，还展示了我们最近制定的CryoSeek研究策略在寻找生物实体和建立碳水化合物结构研究原型方面的潜力。
