Conserved leucine residue in the head region of morbillivirus fusion protein regulates the large conformational change during fusion activity

Plattet, Philippe; Langedijk, J.P.; Zipperle, Ljerka; Vandevelde, Marc; Orvell, C.; Zurbriggen, Andreas (2009). Conserved leucine residue in the head region of morbillivirus fusion protein regulates the large conformational change during fusion activity. Biochemistry, 48(38), pp. 9112-21. Washington, D.C.: American Chemical Society 10.1021/bi9008566

Full text not available from this repository. (Request a copy)

Paramyxovirus cell entry is controlled by the concerted action of two viral envelope glycoproteins, the fusion (F) and the receptor-binding (H) proteins, which together with a cell surface receptor mediate plasma membrane fusion activity. The paramyxovirus F protein belongs to class I viral fusion proteins which typically contain two heptad repeat regions (HR). Particular to paramyxovirus F proteins is a long intervening sequence (IS) located between both HR domains. To investigate the role of the IS domain in regulating fusogenicity, we mutated in the canine distemper virus (CDV) F protein IS domain a highly conserved leucine residue (L372) previously reported to cause a hyperfusogenic phenotype. Beside one F mutant, which elicited significant defects in processing, transport competence, and fusogenicity, all remaining mutants were characterized by enhanced fusion activity despite normal or slightly impaired processing and cell surface targeting. Using anti-CDV-F monoclonal antibodies, modified conformational F states were detected in F mutants compared to the parental protein. Despite these structural differences, coimmunoprecipitation assays did not reveal any drastic modulation in F/H avidity of interaction. However, we found that F mutants had significantly enhanced fusogenicity at low temperature only, suggesting that they folded into conformations requiring less energy to activate fusion. Together, these data provide strong biochemical and functional evidence that the conserved leucine 372 at the base of the HRA coiled-coil of F(wt) controls the stabilization of the prefusogenic state, restraining the conformational switch and thereby preventing extensive cell-cell fusion activity.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Clinical Neurology
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

UniBE Contributor:

Plattet, Philippe; Zipperle, Ljerka; Vandevelde, Marc and Zurbriggen, Andreas

Subjects:

600 Technology > 630 Agriculture

ISSN:

0006-2960

Publisher:

American Chemical Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:25

Last Modified:

16 Feb 2015 15:59

Publisher DOI:

10.1021/bi9008566

Web of Science ID:

000269892000021

URI:

https://boris.unibe.ch/id/eprint/38259 (FactScience: 220779)

Actions (login required)

Edit item Edit item
Provide Feedback