7syz

From Proteopedia

Hendra virus G protein head domain in complex with cross-neutralizing murine antibody hAH1.3

Structural highlights

7syz is a 3 chain structure with sequence from Hendra henipavirus and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.86Å
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 virus (HeV) and Nipah virus (NiV) are deadly zoonotic Henipaviruses (HNVs) responsible for recurrent outbreaks in humans and domestic species of highly fatal (50 to 95%) disease. A HeV variant (HeV-g2) of unprecedented genetic divergence has been identified in two fatally diseased horses, and in two flying fox species in regions of Australia not previously considered at risk for HeV spillover. Given the HeV-g2 divergence from HeV while retaining equivalent pathogenicity and spillover potential, understanding receptor usage and antigenic properties is urgently required to guide One Health biosecurity. Here, we show that the HeV-g2 G glycoprotein shares a conserved receptor tropism with prototypic HeV and that a panel of monoclonal antibodies recognizing the G and F glycoproteins potently neutralizes HeV-g2- and HeV G/F-mediated entry into cells. We determined a crystal structure of the Fab fragment of the hAH1.3 antibody bound to the HeV G head domain, revealing an antigenic site associated with potent cross-neutralization of both HeV-g2 and HeV. Structure-guided formulation of a tetravalent monoclonal antibody (mAb) mixture, targeting four distinct G head antigenic sites, results in potent neutralization of HeV and HeV-g2 and delineates a path forward for implementing multivalent mAb combinations for postexposure treatment of HNV infections.

Potent monoclonal antibody-mediated neutralization of a divergent Hendra virus variant.,Wang Z, Dang HV, Amaya M, Xu Y, Yin R, Yan L, Hickey AC, Annand EJ, Horsburgh BA, Reid PA, Smith I, Eden JS, Xu K, Broder CC, Veesler D Proc Natl Acad Sci U S A. 2022 May 31;119(22):e2122769119. doi: , 10.1073/pnas.2122769119. Epub 2022 May 26. PMID:35617431^[1]

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

References

↑ Wang Z, Dang HV, Amaya M, Xu Y, Yin R, Yan L, Hickey AC, Annand EJ, Horsburgh BA, Reid PA, Smith I, Eden JS, Xu K, Broder CC, Veesler D. Potent monoclonal antibody-mediated neutralization of a divergent Hendra virus variant. Proc Natl Acad Sci U S A. 2022 May 31;119(22):e2122769119. PMID:35617431 doi:10.1073/pnas.2122769119