9MHE
Native tagless Lassa virus spike complex bound to ARN-75039 at pH 8.0
This is a non-PDB format compatible entry.
Summary for 9MHE
| Entry DOI | 10.2210/pdb9mhe/pdb |
| EMDB information | 48275 |
| Descriptor | Glycoprotein G2, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (16 entities in total) |
| Functional Keywords | spike complex, viral protein |
| Biological source | Lassa virus Josiah More |
| Total number of polymer chains | 12 |
| Total formula weight | 337813.52 |
| Authors | Cohen-Dvashi, H.,Katz, M.,Diskin, R. (deposition date: 2024-12-11, release date: 2025-08-27, Last modification date: 2025-09-24) |
| Primary citation | Katz, M.,Cohen-Dvashi, H.,Borni, S.,Ruedas, J.,Henkel, G.,McCormack, K.,Diskin, R. pH-induced conformational changes and inhibition of the Lassa virus spike complex. Cell Host Microbe, 33:1577-1588.e7, 2025 Cited by PubMed Abstract: Lassa virus (LASV) is a devastating human pathogen with no vaccines and limited therapeutics. The LASV class-I spike complex engages target cells via binding its primary host receptor, matriglycan, followed by macropinocytosis and binding of its secondary receptor, lysosomal-associated membrane protein 1 (LAMP1), to trigger virus fusion. This process occurs across multiple pH-dependent steps, but the molecular events remain largely unknown. Through high-resolution structures, we study the pH-induced conformational changes of the spike preceding membrane fusion. We reveal pH-sensitive metal coordination sites that control the integrity of the spike's native state, elucidate a reorganization of the spike's transmembrane region, and provide a mechanism for dissociation from its primary receptor. Using the entry inhibitor ARN-75039, we validate our findings and establish the molecular basis for the binding and function of this investigational drug. These data define the molecular basis for the cell entry of LASV and will promote efforts in combating this virus and potentially related viral pathogens. PubMed: 40897176DOI: 10.1016/j.chom.2025.07.020 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.01 Å) |
Structure validation
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