9N15

Cryo-EM structure of HCoV-HKU1 glycoprotein D1 Domain in complex with 9OAc-GD3(mutant T31VPR34 to GGGG)

これはPDB形式変換不可エントリーです。

9N15 の概要

• エントリーDOI: 10.2210/pdb9n15/pdb
• EMDBエントリー: 48806
• 分子名称: Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: hcov-hku1 spike glycoprotein ectodomain, proline stablized, viral protein
• 由来する生物種: Human coronavirus HKU1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 154261.94

構造登録者

Jin, M.,Rini, J.M. (登録日: 2025-01-24, 公開日: 2025-05-14, 最終更新日: 2025-05-21)

主引用文献

Jin, M.,Hassan, Z.,Li, Z.,Liu, Y.,Marakhovskaia, A.,Wong, A.H.M.,Forman, A.,Nitz, M.,Gilbert, M.,Yu, H.,Chen, X.,Rini, J.M.
Human coronavirus HKU1 spike structures reveal the basis for sialoglycan specificity and carbohydrate-promoted conformational changes.
Nat Commun, 16:4158-4158, 2025

PubMed Abstract: The human coronavirus HKU1 uses both sialoglycoconjugates and the protein transmembrane serine protease 2 (TMPRSS2) as receptors. Carbohydrate binding leads to the spike protein up conformation required for TMPRSS2 binding, an outcome suggesting a distinct mechanism for driving fusion of the viral and host cell membranes. Nevertheless, the conformational changes promoted by carbohydrate binding have not been fully elucidated and the basis for HKU1's carbohydrate binding specificity remains unknown. Reported here are high resolution cryo-EM structures of the HKU1 spike protein trimer in its apo form and in complex with the carbohydrate moiety of a candidate carbohydrate receptor, the 9-O-acetylated GD3 ganglioside. The structures show that the spike monomer can exist in four discrete conformational states and that progression through them would promote the up conformation upon carbohydrate binding. We also show that a six-amino-acid insert is a determinant of HKU1's specificity for gangliosides containing a 9-O-acetylated α2-8-linked disialic acid moiety and that HKU1 shows weak affinity for the 9-O-acetylated sialic acids found on decoy receptors such as mucins.

PubMed: 40324974
DOI: 10.1038/s41467-025-59137-y

実験手法

ELECTRON MICROSCOPY (3.2 Å)