{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:46Z","timestamp":1792789126232,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T00:00:00Z","timestamp":1766275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202517"],"award-info":[{"award-number":["82202517"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shenzhen Science and Technology Program","award":["RCYX20231211090342048"],"award-info":[{"award-number":["RCYX20231211090342048"]}]},{"name":"Shenzhen Medical Research Fund","award":["B2402043"],"award-info":[{"award-number":["B2402043"]}]},{"name":"Shenzhen Medical Research Fund","award":["E24010012"],"award-info":[{"award-number":["E24010012"]}]},{"name":"Major Talent Recruitment Program of Guangdong Province","award":["2021QNO2Y167"],"award-info":[{"award-number":["2021QNO2Y167"]}]},{"name":"Scientific Research and Innovation Project of Medical Discipline","award":["G030410001"],"award-info":[{"award-number":["G030410001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The Rift Valley fever virus (RVFV) is a highly pathogenic, mosquito-borne zoonotic virus that poses a significant risk to livestock, human health, and global public health security. Although RVFV is classified by the World Health Organization (WHO) as a priority pathogen with epidemic potential, no licensed vaccines or effective antiviral therapies are currently available. A limited understanding of the molecular mechanisms of RVFV entry has hindered therapeutic development. Here, we elucidate the molecular basis by which the RVFV envelope glycoprotein Gn recognizes its receptor, low-density lipoprotein receptor-related protein 1 (LRP1). Bio-layer interferometry (BLI) demonstrates that full-length LRP1 directly binds the head domain of Gn with nanomolar affinity in a Ca2+-dependent manner. Both LRP1 clusters II (CL II) and IV (CL IV) independently interact with Gn, with CL IV exhibiting stronger affinity, indicating a multivalent recognition mode. Structural modeling using AlphaFold 3 reveals pronounced charge complementarity between basic residues on Gn and acidic, Ca2+-coordinated pockets within LRP1. Mutations in key acidic residues in CL IV greatly reduced Gn binding, confirming the essential roles of Ca2+ coordination and electrostatic interactions. Collectively, our findings define a Ca2+-stabilized, electrostatically driven mechanism for RVFV Gn recognition by LRP1, providing molecular insight into viral entry and a structural framework for the rational design of vaccines and antiviral therapeutics.<\/jats:p>","DOI":"10.3390\/biom16010014","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T07:01:33Z","timestamp":1766386893000},"page":"14","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["LRP1 Interacts with the Rift Valley Fever Virus Glycoprotein Gn via a Calcium-Dependent Multivalent Electrostatic Mechanism"],"prefix":"10.3390","volume":"16","author":[{"given":"Haonan","family":"Yang","sequence":"first","affiliation":[{"name":"SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"Key University Laboratory of Metabolism and Health of Guangdong, Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojin","family":"Chen","sequence":"additional","affiliation":[{"name":"SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"Key University Laboratory of Metabolism and Health of Guangdong, Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5673-0913","authenticated-orcid":false,"given":"Wanyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People\u2019s Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen 518112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7122-6547","authenticated-orcid":false,"given":"Renhong","family":"Yan","sequence":"additional","affiliation":[{"name":"SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China"},{"name":"Key University Laboratory of Metabolism and Health of Guangdong, Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1007\/s11262-025-02164-0","article-title":"Recent advances in treatment and detection of Rift Valley fever virus: A comprehensive overview","volume":"61","author":"Yekanipour","year":"2025","journal-title":"Virus Genes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1002\/path.1700340418","article-title":"Enzootic Hepatitis or Rift Valley Fever. 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