CryoSeek II: Cryo-EM analysis of glycofibrils from freshwater reveals well-structured glycans coating linear tetrapeptide repeats

T Tongtong Wang (School of Chemical Science and Engineering, Tongji University, 1239 Siping Rd, Shanghai, 200092, China) W Wenze Huang (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) K Kui Xu (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) Y Yitong Sun (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) Q Qiangfeng Cliff Zhang C Chuangye Yan (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, China.) Z Zhangqiang Li (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) N Nieng Yan

Abstract

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.

Article Details

Volume / Issue Vol. 122, Issue 1
Published January 07, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (8)

T

Tongtong Wang

School of Chemical Science and Engineering, Tongji University, 1239 Siping Rd, Shanghai, 200092, China

W

Wenze Huang

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

K

Kui Xu

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

Y

Yitong Sun

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

Q

Qiangfeng Cliff Zhang

C

Chuangye Yan

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, China.

Z

Zhangqiang Li

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

N

Nieng Yan