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<p>Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease and poses a significant public health threat through severe neurological complications in pediatric cases. P-selectin glycoprotein ligand-1 (PSGL-1) functions as an attachment factor, yet the structural basis of PSGL-1 recognition on the EV-A71 capsid has remained undefined. Here, we use cryo-EM to compare a PSGL-1–non-binding EV-A71 strain (EV-V) with a PSGL-1–binding strain (EV-R) and analyzeEV-R particles incubated with a sulfated 20-residue PSGL-1 N-terminal peptide (sPSGL-1; residues 42–61). In EV-R, a VP1-145 substitution disrupts the interprotomer E145–K244 interaction, repositions K244, and increases local electrostatic potential at the fivefold vertex. A fivefold-focused, symmetry-relaxed (C1; no symmetry imposed) 2.38 Å reconstruction reveals low-occupancy, vertex-adjacent densities associated with sPSGL-1 incubation, including a locally interpretable density feature consistent with an aromatic ring near VP1 K244, together with localized structural differences in VP1 loops and pocket-adjacent regions. The pocket factor and VP4 remain present, and electrostatic mapping localizes this signal within a lysine-rich vertex cleft. These observations are consistent with localized fivefold-vertex priming without evidence for an uncoating-associated A-particle transition within the compact/closed population analyzed.</p>

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Sulfated PSGL-1 primes the enterovirus A71 fivefold vertex for localized remodeling

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月3日

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  • Ya-Na Wu,
  • Yen-Hung Chow,
  • Wen-Shuo Kuo,
  • Chun-Hsiung Wang,
  • Ching-Kun Chang,
  • Guan-Wen Chen,
  • Nai-Hsiang Chung,
  • Yu-Shan Hsieh,
  • Ying-Chin Chen,
  • Ying-Hua Chuang,
  • Shu-Ling Yu,
  • Tzu-Chi Chuang,
  • Shang-Rung Wu

摘要

Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease and poses a significant public health threat through severe neurological complications in pediatric cases. P-selectin glycoprotein ligand-1 (PSGL-1) functions as an attachment factor, yet the structural basis of PSGL-1 recognition on the EV-A71 capsid has remained undefined. Here, we use cryo-EM to compare a PSGL-1–non-binding EV-A71 strain (EV-V) with a PSGL-1–binding strain (EV-R) and analyzeEV-R particles incubated with a sulfated 20-residue PSGL-1 N-terminal peptide (sPSGL-1; residues 42–61). In EV-R, a VP1-145 substitution disrupts the interprotomer E145–K244 interaction, repositions K244, and increases local electrostatic potential at the fivefold vertex. A fivefold-focused, symmetry-relaxed (C1; no symmetry imposed) 2.38 Å reconstruction reveals low-occupancy, vertex-adjacent densities associated with sPSGL-1 incubation, including a locally interpretable density feature consistent with an aromatic ring near VP1 K244, together with localized structural differences in VP1 loops and pocket-adjacent regions. The pocket factor and VP4 remain present, and electrostatic mapping localizes this signal within a lysine-rich vertex cleft. These observations are consistent with localized fivefold-vertex priming without evidence for an uncoating-associated A-particle transition within the compact/closed population analyzed.