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Peer-reviewedCC BY-NC 4.0Science Advances

On-virion structural dynamics reveal temperature- and receptor-coordinated activation of an alphacoronavirus spike

  • Jiaming Liang1,2,3,4,5
  • Cheng Peng1,2,3,4,5
  • Ruixiao Tan1,2,3,4,5
  • Yutong Song1,2,3,4,5
  • Zheyuan Zhang1,2,3,4,5
  • Jinfang Yu2,5,6
  • Xinquan Wang2,5,6
  • Sai Li1,2,3,4,5
6 affiliations
  1. 1State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China.
  2. 2Beijing Frontier Research Center for Biological Structure, Tsinghua University, Beijing 100084, China.
  3. 3Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
  4. 4Center for Life Sciences and Artificial Intelligence, Tsinghua University, Beijing 100084, China.
  5. 5School of Life Sciences, Tsinghua University, Beijing 100084, China.
  6. 6The Ministry of Education Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China.
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Abstract

Human alphacoronaviruses primarily infect the human upper respiratory tract, yet how temperature and receptor-binding coordinate viral spike (S) protein activation remains unclear. Using cryo-electron tomography and subtomogram averaging, we directly visualized the structural dynamics of S on human coronavirus 229E (HCoV-229E) virions under physiologically relevant temperatures and in the presence of the host receptor human aminopeptidase N (hAPN). We identified two prefusion S2 conformations, compact and loose, that interconvert reversibly by temperature, revealing intrinsic S2 “breathing” on virions. Receptor-binding domain (RBD)-up conformations are rare on apo virions but are promoted at 33°C and stabilized upon receptor binding. hAPN can bind bivalently to neighboring S, forming Gemini S-hAPN complexes. Receptor incubation further promotes conversion from prefusion to postfusion S, an effect enhanced at 33°C. Together, our results demonstrate an optimized temperature for the HCoV-229E viral fitness, and establish temperature and receptor binding as synergistic regulators of alphacoronavirus S activation. These findings provide a structural framework for understanding alphacoronavirus infectivity.

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Cite

BibTeXRIS
BibTeX
@article{liang2026onvirion,
  title = {{On-virion structural dynamics reveal temperature- and receptor-coordinated activation of an alphacoronavirus spike}},
  author = {Jiaming Liang and Cheng Peng and Ruixiao Tan and Yutong Song and Zheyuan Zhang and Jinfang Yu and Xinquan Wang and Sai Li},
  journal = {Science Advances},
  year = {2026},
  month = nov,
  doi = {10.1126/sciadv.aef6880},
  url = {https://www.science.org/doi/abs/10.1126/sciadv.aef6880},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - On-virion structural dynamics reveal temperature- and receptor-coordinated activation of an alphacoronavirus spike
AU  - Jiaming Liang
AU  - Cheng Peng
AU  - Ruixiao Tan
AU  - Yutong Song
AU  - Zheyuan Zhang
AU  - Jinfang Yu
AU  - Xinquan Wang
AU  - Sai Li
PY  - 2026
DA  - 2026/11/04
JO  - Science Advances
DO  - 10.1126/sciadv.aef6880
UR  - https://www.science.org/doi/abs/10.1126/sciadv.aef6880
AB  - Human alphacoronaviruses primarily infect the human upper respiratory tract, yet how temperature and receptor-binding coordinate viral spike (S) protein activation remains unclear. Using cryo-electron tomography and subtomogram averaging, we directly visualized the structural dynamics of S on human coronavirus 229E (HCoV-229E) virions under physiologically relevant temperatures and in the presence of the host receptor human aminopeptidase N (hAPN). We identified two prefusion S2 conformations, compact and loose, that interconvert reversibly by temperature, revealing intrinsic S2 “breathing” on virions. Receptor-binding domain (RBD)-up conformations are rare on apo virions but are promoted at 33°C and stabilized upon receptor binding. hAPN can bind bivalently to neighboring S, forming Gemini S-hAPN complexes. Receptor incubation further promotes conversion from prefusion to postfusion S, an effect enhanced at 33°C. Together, our results demonstrate an optimized temperature for the HCoV-229E viral fitness, and establish temperature and receptor binding as synergistic regulators of alphacoronavirus S activation. These findings provide a structural framework for understanding alphacoronavirus infectivity.
SN  - 2375-2548
ER  -