6vy6

From Proteopedia

Crystal structure of Hendra receptor binding protein head domain in complex with human neutralizing antibody HENV-26

Structural highlights

6vy6 is a 3 chain structure with sequence from Henipavirus hendraense and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GLYCP_HENDH Attaches the virus to sialic acid-containing cell receptors and thereby initiating infection. Binding of glycoprotein G to the receptor induces a conformational change that allows the F protein to trigger virion/cell membranes fusion (By similarity).

Publication Abstract from PubMed

Hendra (HeV) and Nipah (NiV) viruses are emerging zoonotic pathogens in the Henipavirus genus causing outbreaks of disease with very high case fatality rates. Here, we report the first naturally occurring human monoclonal antibodies (mAbs) against HeV receptor binding protein (RBP). All isolated mAbs neutralized HeV, and some also neutralized NiV. Epitope binning experiments identified five major antigenic sites on HeV-RBP. Animal studies demonstrated that the most potent cross-reactive neutralizing mAbs, HENV-26 and HENV-32, protected ferrets in lethal models of infection with NiV Bangladesh 3 days after exposure. We solved the crystal structures of mAb HENV-26 in complex with both HeV-RBP and NiV-RBP and of mAb HENV-32 in complex with HeV-RBP. The studies reveal diverse sites of vulnerability on RBP recognized by potent human mAbs that inhibit virus by multiple mechanisms. These studies identify promising prophylactic antibodies and define protective epitopes that can be used in rational vaccine design.

Potent Henipavirus Neutralization by Antibodies Recognizing Diverse Sites on Hendra and Nipah Virus Receptor Binding Protein.,Dong J, Cross RW, Doyle MP, Kose N, Mousa JJ, Annand EJ, Borisevich V, Agans KN, Sutton R, Nargi R, Majedi M, Fenton KA, Reichard W, Bombardi RG, Geisbert TW, Crowe JE Jr Cell. 2020 Dec 10;183(6):1536-1550.e17. doi: 10.1016/j.cell.2020.11.023. PMID:33306954^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dong J, Cross RW, Doyle MP, Kose N, Mousa JJ, Annand EJ, Borisevich V, Agans KN, Sutton R, Nargi R, Majedi M, Fenton KA, Reichard W, Bombardi RG, Geisbert TW, Crowe JE Jr. Potent Henipavirus Neutralization by Antibodies Recognizing Diverse Sites on Hendra and Nipah Virus Receptor Binding Protein. Cell. 2020 Dec 10;183(6):1536-1550.e17. PMID:33306954 doi:10.1016/j.cell.2020.11.023