5EVM

Crystal Structure of Nipah Virus Fusion Glycoprotein in the Prefusion State

Summary for 5EVM

• Entry DOI: 10.2210/pdb5evm/pdb
• Descriptor: Fusion glycoprotein F0, alpha-D-mannopyranose-(1-2)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: fusion protein, nipah, prefusion, paramyxovirus, henipavirus, viral protein
• Biological source: Nipah virus
• Total number of polymer chains: 6
• Total formula weight: 362586.58

Authors

Xu, K.,Nikolov, D.B. (deposition date: 2015-11-20, release date: 2015-12-16, Last modification date: 2024-11-20)

Primary citation

Xu, K.,Chan, Y.P.,Bradel-Tretheway, B.,Akyol-Ataman, Z.,Zhu, Y.,Dutta, S.,Yan, L.,Feng, Y.,Wang, L.F.,Skiniotis, G.,Lee, B.,Zhou, Z.H.,Broder, C.C.,Aguilar, H.C.,Nikolov, D.B.
Crystal Structure of the Pre-fusion Nipah Virus Fusion Glycoprotein Reveals a Novel Hexamer-of-Trimers Assembly.
Plos Pathog., 11:e1005322-e1005322, 2015

PubMed Abstract: Nipah virus (NiV) is a paramyxovirus that infects host cells through the coordinated efforts of two envelope glycoproteins. The G glycoprotein attaches to cell receptors, triggering the fusion (F) glycoprotein to execute membrane fusion. Here we report the first crystal structure of the pre-fusion form of the NiV-F glycoprotein ectodomain. Interestingly this structure also revealed a hexamer-of-trimers encircling a central axis. Electron tomography of Nipah virus-like particles supported the hexameric pre-fusion model, and biochemical analyses supported the hexamer-of-trimers F assembly in solution. Importantly, structure-assisted site-directed mutagenesis of the interfaces between F trimers highlighted the functional relevance of the hexameric assembly. Shown here, in both cell-cell fusion and virus-cell fusion systems, our results suggested that this hexamer-of-trimers assembly was important during fusion pore formation. We propose that this assembly would stabilize the pre-fusion F conformation prior to cell attachment and facilitate the coordinated transition to a post-fusion conformation of all six F trimers upon triggering of a single trimer. Together, our data reveal a novel and functional pre-fusion architecture of a paramyxoviral fusion glycoprotein.

PubMed: 26646856
DOI: 10.1371/journal.ppat.1005322

Experimental method

X-RAY DIFFRACTION (3.367 Å)