5MDM

Structural intermediates in the fusion associated transition of vesiculovirus glycoprotein

Summary for 5MDM

• Entry DOI: 10.2210/pdb5mdm/pdb
• Descriptor: Glycoprotein, 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)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: class iii viral fusion glycoprotein, viral protein
• Biological source: Chandipura virus (CHPV)
• Cellular location: Virion membrane ; Single-pass type I membrane protein : P13180
• Total number of polymer chains: 4
• Total formula weight: 188769.08

Authors

Baquero, E.,Albertini, A.A.,Gaudin, Y.,Bressanelli, S. (deposition date: 2016-11-11, release date: 2016-12-14, Last modification date: 2024-01-17)

Primary citation

Baquero, E.,Albertini, A.A.,Raux, H.,Abou-Hamdan, A.,Boeri-Erba, E.,Ouldali, M.,Buonocore, L.,Rose, J.K.,Lepault, J.,Bressanelli, S.,Gaudin, Y.
Structural intermediates in the fusion-associated transition of vesiculovirus glycoprotein.
EMBO J., 36:679-692, 2017

PubMed Abstract: Vesiculoviruses enter cells by membrane fusion, driven by a large, low-pH-induced, conformational change in the fusion glycoprotein G that involves transition from a trimeric pre-fusion toward a trimeric post-fusion state via monomeric intermediates. Here, we present the structure of the G fusion protein at intermediate pH for two vesiculoviruses, vesicular stomatitis virus (VSV) and Chandipura virus (CHAV), which is responsible for deadly encephalopathies. First, a CHAV G crystal structure shows two intermediate conformations forming a flat dimer of heterodimers. On virions, electron microscopy (EM) and tomography reveal monomeric spikes similar to one of the crystal conformations. In solution, mass spectrometry shows dimers of G. Finally, mutations at a dimer interface, involving fusion domains associated in an antiparallel manner to form an intermolecular β-sheet, affect G fusion properties. The location of the compensatory mutations restoring fusion activity strongly suggests that this interface is functionally relevant. This work reveals the range of G structural changes and suggests that G monomers can re-associate, through antiparallel interactions between fusion domains, into dimers that play a role at some early stage of the fusion process.

PubMed: 28188244
DOI: 10.15252/embj.201694565

Experimental method

X-RAY DIFFRACTION (2.998 Å)