8DDK

CCHFV GP38 Hoti/Kosovo bound with CC5_17

Summary for 8DDK

• Entry DOI: 10.2210/pdb8ddk/pdb
• Related: 8DC5 8DCY
• Descriptor: Heavy Chain CC5-17, Light Chain CC5_17, Envelopment polyprotein, ... (6 entities in total)
• Functional Keywords: crimean-congo hemorrhagic fever, cchfv, glycoprotein, gp38, hoti, kosovo, 13g8, fab, viral protein, cc5-17, mab
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 82181.05

Authors

Durie, I.A.,Bergeron, E.,Pegan, S.D.,McGuire, J. (deposition date: 2022-06-18, release date: 2022-12-14, Last modification date: 2024-10-09)

Primary citation

Durie, I.A.,Tehrani, Z.R.,Karaaslan, E.,Sorvillo, T.E.,McGuire, J.,Golden, J.W.,Welch, S.R.,Kainulainen, M.H.,Harmon, J.R.,Mousa, J.J.,Gonzalez, D.,Enos, S.,Koksal, I.,Yilmaz, G.,Karakoc, H.N.,Hamidi, S.,Albay, C.,Spengler, J.R.,Spiropoulou, C.F.,Garrison, A.R.,Sajadi, M.M.,Bergeron, E.,Pegan, S.D.
Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus.
Nat Commun, 13:7298-7298, 2022

PubMed Abstract: Crimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains.

PubMed: 36435827
DOI: 10.1038/s41467-022-34923-0

Experimental method

X-RAY DIFFRACTION (3.86 Å)