Structural rearrangements of the central region of the morbillivirus attachment protein stalk domain trigger F protein refolding for membrane fusion

Ader, Nadine; Brindley, M. A.; Avila, Mislay; Origgi, Francesco; Langedijk, J. P.; Orvell, C.; Vandevelde, Marc; Zurbriggen, Andreas; Plemper, R. K.; Plattet, Philippe (2012). Structural rearrangements of the central region of the morbillivirus attachment protein stalk domain trigger F protein refolding for membrane fusion. Journal of biological chemistry, 287(20), pp. 16324-34. American Society for Biochemistry and Molecular Biology 10.1074/jbc.M112.342493

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It is unknown how receptor binding by the paramyxovirus attachment proteins (HN, H, or G) triggers the fusion (F) protein to fuse with the plasma membrane for cell entry. H-proteins of the morbillivirus genus consist of a stalk ectodomain supporting a cuboidal head; physiological oligomers consist of non-covalent dimer-of-dimers. We report here the successful engineering of intermolecular disulfide bonds within the central region (residues 91-115) of the morbillivirus H-stalk; a sub-domain that also encompasses the putative F-contacting section (residues 111-118). Remarkably, several intersubunit crosslinks abrogated membrane fusion, but bioactivity was restored under reducing conditions. This phenotype extended equally to H proteins derived from virulent and attenuated morbillivirus strains and was independent of the nature of the contacted receptor. Our data reveal that the morbillivirus H-stalk domain is composed of four tightly-packed subunits. Upon receptor binding, these subunits structurally rearrange, possibly inducing conformational changes within the central region of the stalk, which, in turn, promote fusion. Given that the fundamental architecture appears conserved among paramyxovirus attachment protein stalk domains, we predict that these motions may act as a universal paramyxovirus F-triggering mechanism.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > NeuroCenter
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 Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Center for Fish and Wildlife Health (FIWI)

UniBE Contributor:

Ebert, Nadine; Avila Sanchez, Mislay; Origgi, Francesco; Vandevelde, Marc; Zurbriggen, Andreas and Plattet, Philippe

Subjects:

600 Technology > 630 Agriculture

ISSN:

0021-9258

Publisher:

American Society for Biochemistry and Molecular Biology

Language:

English

Submitter:

Andrea Stettler

Date Deposited:

21 Jan 2014 15:10

Last Modified:

31 Mar 2016 16:46

Publisher DOI:

10.1074/jbc.M112.342493

PubMed ID:

22431728

Uncontrolled Keywords:

Animals, Cercopithecus aethiops, Humans, Membrane, Fusion/*physiology, Morbillivirus/genetics/*metabolism *Protein Folding, Protein Structure, Tertiary, Vero Cells, Viral Fusion Proteins/genetics/*metabolism, *Virus, Internalization

BORIS DOI:

10.7892/boris.40434

URI:

https://boris.unibe.ch/id/eprint/40434

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