4UF7

Ghanaian henipavirus (Gh-M74a) attachment glycoprotein in complex with human ephrinB2

Summary for 4UF7

• Entry DOI: 10.2210/pdb4uf7/pdb
• Descriptor: GLYCOPROTEIN, EPHRIN-B2, SULFATE ION, ... (7 entities in total)
• Functional Keywords: viral protein-immune system complex, gh-m74a, hendra virus, nipah virus, viral attachment, glycoprotein, paramyxovirus, ghv-g, niv-g, hev-g, hnv, hnv-g, viral protein/immune system
• Biological source: BAT PARAMYXOVIRUS EID_HEL/GH-M74A/GHA/2009 (GHANA VIRUS); More
• Total number of polymer chains: 4
• Total formula weight: 143847.48

Authors

Lee, B.,Pernet, O.,Ahmed, A.A.,Zeltina, A.,Beaty, S.M.,Bowden, T.A. (deposition date: 2015-03-13, release date: 2015-04-01, Last modification date: 2023-12-20)

Primary citation

Lee, B.,Pernet, O.,Ahmed, A.A.,Zeltina, A.,Beaty, S.M.,Bowden, T.A.
Molecular Recognition of Human Ephrinb2 Cell Surface Receptor by an Emergent African Henipavirus.
Proc.Natl.Acad.Sci.USA, 112:E2156-, 2015

PubMed Abstract: The discovery of African henipaviruses (HNVs) related to pathogenic Hendra virus (HeV) and Nipah virus (NiV) from Southeast Asia and Australia presents an open-ended health risk. Cell receptor use by emerging African HNVs at the stage of host-cell entry is a key parameter when considering the potential for spillover and infection of human populations. The attachment glycoprotein from a Ghanaian bat isolate (GhV-G) exhibits <30% sequence identity with Asiatic NiV-G/HeV-G. Here, through functional and structural analysis of GhV-G, we show how this African HNV targets the same human cell-surface receptor (ephrinB2) as the Asiatic HNVs. We first characterized this virus-receptor interaction crystallographically. Compared with extant HNV-G-ephrinB2 structures, there was significant structural variation in the six-bladed β-propeller scaffold of the GhV-G receptor-binding domain, but not the Greek key fold of the bound ephrinB2. Analysis revealed a surprisingly conserved mode of ephrinB2 interaction that reflects an ongoing evolutionary constraint among geographically distal and phylogenetically divergent HNVs to maintain the functionality of ephrinB2 recognition during virus-host entry. Interestingly, unlike NiV-G/HeV-G, we could not detect binding of GhV-G to ephrinB3. Comparative structure-function analysis further revealed several distinguishing features of HNV-G function: a secondary ephrinB2 interaction site that contributes to more efficient ephrinB2-mediated entry in NiV-G relative to GhV-G and cognate residues at the very C terminus of GhV-G (absent in Asiatic HNV-Gs) that are vital for efficient receptor-induced fusion, but not receptor binding per se. These data provide molecular-level details for evaluating the likelihood of African HNVs to spill over into human populations.

PubMed: 25825759
DOI: 10.1073/PNAS.1501690112

Experimental method

X-RAY DIFFRACTION (1.7 Å)