Cryo-EM structure of the prefusion state of canine distemper virus fusion protein ectodomain.

Kalbermatter, David; Shrestha, Neeta; Gall, Flavio M.; Wyss, Marianne; Riedl, Rainer; Plattet, Philippe; Fotiadis, Dimitrios (2020). Cryo-EM structure of the prefusion state of canine distemper virus fusion protein ectodomain. Journal of structural biology: X, 4, p. 100021. Elsevier 10.1016/j.yjsbx.2020.100021

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Measles virus (MeV) and canine distemper virus (CDV), two members of the Morbillivirus genus, are still causing important global diseases of humans and animals, respectively. To enter target cells, morbilliviruses rely on an envelope-anchored machinery, which is composed of two interacting glycoproteins: a tetrameric receptor binding (H) protein and a trimeric fusion (F) protein. To execute membrane fusion, the F protein initially adopts a metastable, prefusion state that refolds into a highly stable postfusion conformation as the result of a finely coordinated activation process mediated by the H protein. Here, we employed cryo-electron microscopy (cryo-EM) and single particle reconstruction to elucidate the structure of the prefusion state of the CDV F protein ectodomain (solF) at 4.3 Å resolution. Stabilization of the prefusion solF trimer was achieved by fusing the GCNt trimerization sequence at the C-terminal protein region, and expressing and purifying the recombinant protein in the presence of a morbilliviral fusion inhibitor class compound. The three-dimensional cryo-EM map of prefusion CDV solF in complex with the inhibitor clearly shows density for the ligand at the protein binding site suggesting common mechanisms of membrane fusion activation and inhibition employed by different morbillivirus members.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research

UniBE Contributor:

Kalbermatter, David; Shrestha, Neeta; Wyss, Marianne; Plattet, Philippe and Fotiadis, Dimitrios José

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2590-1524

Publisher:

Elsevier

Language:

English

Submitter:

Barbara Järmann-Bangerter

Date Deposited:

01 Sep 2020 11:52

Last Modified:

13 Mar 2021 12:54

Publisher DOI:

10.1016/j.yjsbx.2020.100021

PubMed ID:

32647825

Uncontrolled Keywords:

CDV, canine distemper virus Canine distemper virus Cryo-electron microscopy FP, fusion peptide Fusion protein MeV, measles virus Morbillivirus cell entry Single particle reconstruction cryo-EM, cryo-electron microscopy

BORIS DOI:

10.7892/boris.146126

URI:

https://boris.unibe.ch/id/eprint/146126

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