Work

Atomic resolution structure of human papillomavirus bound to heparin

Year: 2026

Type: article

Abstract: Human papillomavirus (HPV) is a significant health burden and leading cause of virus-induced cancers. The mechanisms of HPV receptor binding and host entry are not completely understood, although it is known that heparan sulfate proteoglycans (HSPGs) mediate entry. HPV16 quasivirus, composed of L1 and L2 capsid proteins with a packaged cottontail rabbit papillomavirus genome was incubated with heparin. The complex was vitrified, and data were collected for cryoEM single particle analysis. Subparticles were extracted and hexavalent and pentavalent capsomers were refined separately. Here we present the resulting 1.9 Å resolution structure, with heparin visualized around the capsomer at the icosahedral fivefold vertex. A model of the asymmetric unit was built unambiguously into the atomic resolution cryoEM map. Hydrogen bonds are predicted between L1 N-terminal regions, which are supported by molecular dynamics. The heparin binding site was identified, along with local L1 conformational changes and global flexibility changes. These changes induced by heparin binding likely reflect the structure of HPV during early stages of entry and provide a framework for future HPV biochemical, genetic, and biophysical studies.

Source: Nature Communications

DOI: 10.1038/s41467-026-77019-9

Authors: Caroline H. Langley, Daniel J. Goetschius, Santiago Antolínez, Ebere Precious Orji, Carol M. Bator, Sarah A. Brendle, Neil D. Christensen, Jodi A. Hadden-Perilla, Susan L. Hafenstein

Institutions: University of Minnesota, Pennsylvania State University, University of Delaware, Mayo Clinic

Language: English

Topic: Advanced Electron Microscopy Techniques and Applications

Subfield: Structural Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990

Funders: National Science Foundation, Pennsylvania Department of Health, Purdue University, National Institutes of Health, NIH Office of the Director, Office of Advanced Cyberinfrastructure

Awards: G1453181110, Track 4: Advanced CI Coordination Ecosystem: Monitoring and Measurement Services, G1927003939, G2299875479, G2888034965, G2985829424, Discovery of Molecular Probes and Therapeutic Leads, Administrative Supplement on HPV, G3115553707, MRI: Acquisition of a Big Data and High Performance Computing System to Catalyze Delaware Research and Education, G3185749182, G34258105, G3562386289, Track 1: ACCESS Resource Allocations Marketplace and Platform Services (RAMPS), G4010157413, G4275568664, G446482738, ACO: An Open CI Ecosystem to Advance Scientific Discovery (OpenCI), G4943145253, Track 3: COre National Ecosystem for CyberinfrasTructure (CONECT), G5156331529, G5367127336, G5464919783, G7008713262, G731264315, G7526614437, Track 2: Customized Multi-tier Assistance, Training, and Computational Help (MATCH) for End User ACCESS to CI, G8499740153, G878072758, G9000093202, G9000176595, G9000365068

OpenAlex ID: W7204264443

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