7QQB

Crystal structure of the envelope glycoprotein complex of Puumala virus in complex with the scFv fragment of the broadly neutralizing human antibody ADI-42898

This is a non-PDB format compatible entry.

Summary for 7QQB

• Entry DOI: 10.2210/pdb7qqb/pdb
• Descriptor: Envelope polyprotein, Single Chain Variable Fragment (scFv) of ADI-42898, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: hantavirus, neutralizing antibodies, fusion proteins, bunyavirus, viral protein
• Biological source: Puumala orthohantavirus; More
• Total number of polymer chains: 4
• Total formula weight: 256476.68

Authors

Serris, A.,Rey, F.A.,Guardado-Calvo, P. (deposition date: 2022-01-07, release date: 2023-06-21, Last modification date: 2024-10-23)

Primary citation

Mittler, E.,Serris, A.,Esterman, E.S.,Florez, C.,Polanco, L.C.,O'Brien, C.M.,Slough, M.M.,Tynell, J.,Groning, R.,Sun, Y.,Abelson, D.M.,Wec, A.Z.,Haslwanter, D.,Keller, M.,Ye, C.,Bakken, R.R.,Jangra, R.K.,Dye, J.M.,Ahlm, C.,Rappazzo, C.G.,Ulrich, R.G.,Zeitlin, L.,Geoghegan, J.C.,Bradfute, S.B.,Sidoli, S.,Forsell, M.N.E.,Strandin, T.,Rey, F.A.,Herbert, A.S.,Walker, L.M.,Chandran, K.,Guardado-Calvo, P.
Structural and mechanistic basis of neutralization by a pan-hantavirus protective antibody.
Sci Transl Med, 15:eadg1855-eadg1855, 2023

PubMed Abstract: Emerging rodent-borne hantaviruses cause severe diseases in humans with no approved vaccines or therapeutics. We recently isolated a monoclonal broadly neutralizing antibody (nAb) from a Puumala virus-experienced human donor. Here, we report its structure bound to its target, the Gn/Gc glycoprotein heterodimer comprising the viral fusion complex. The structure explains the broad activity of the nAb: It recognizes conserved Gc fusion loop sequences and the main chain of variable Gn sequences, thereby straddling the Gn/Gc heterodimer and locking it in its prefusion conformation. We show that the nAb's accelerated dissociation from the divergent Andes virus Gn/Gc at endosomal acidic pH limits its potency against this highly lethal virus and correct this liability by engineering an optimized variant that sets a benchmark as a candidate pan-hantavirus therapeutic.

PubMed: 37315110
DOI: 10.1126/scitranslmed.adg1855

Experimental method

X-RAY DIFFRACTION (2.6 Å)