7A59

Crimean-Congo Hemorrhagic Fever Virus Envelope Glycoprotein Gc W1191H/W1197A/W1199A Mutant in Postfusion Conformation (Orthorhombic Crystal Form)

Summary for 7A59

• Entry DOI: 10.2210/pdb7a59/pdb
• Descriptor: Envelopment polyprotein, alpha-D-mannopyranose-(1-6)-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, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: virus entry, class ii membrane fusion protein, viral protein
• Biological source: Crimean-Congo hemorrhagic fever virus strain IbAr10200 (CCHFV)
• Total number of polymer chains: 3
• Total formula weight: 181257.32

Authors

Hellert, J.,Guardado-Calvo, P.,Rey, F.A. (deposition date: 2020-08-20, release date: 2021-10-06, Last modification date: 2024-10-23)

Primary citation

Mishra, A.K.,Hellert, J.,Freitas, N.,Guardado-Calvo, P.,Haouz, A.,Fels, J.M.,Maurer, D.P.,Abelson, D.M.,Bornholdt, Z.A.,Walker, L.M.,Chandran, K.,Cosset, F.L.,McLellan, J.S.,Rey, F.A.
Structural basis of synergistic neutralization of Crimean-Congo hemorrhagic fever virus by human antibodies.
Science, 375:104-109, 2022

PubMed Abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-borne zoonotic virus, with a 30% case fatality rate in humans. Structural information is lacking in regard to the CCHFV membrane fusion glycoprotein Gc—the main target of the host neutralizing antibody response—as well as antibody–mediated neutralization mechanisms. We describe the structure of prefusion Gc bound to the antigen-binding fragments (Fabs) of two neutralizing antibodies that display synergy when combined, as well as the structure of trimeric, postfusion Gc. The structures show the two Fabs acting in concert to block membrane fusion, with one targeting the fusion loops and the other blocking Gc trimer formation. The structures also revealed the neutralization mechanism of previously reported antibodies against CCHFV, providing the molecular underpinnings essential for developing CCHFV–specific medical countermeasures for epidemic preparedness.

PubMed: 34793197
DOI: 10.1126/science.abl6502

Experimental method

X-RAY DIFFRACTION (2.197 Å)