Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein
- 10 September 2012
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 109 (41), 16672-16677
- https://doi.org/10.1073/pnas.1213802109
Abstract
The paramyxovirus parainfluenza virus 5 (PIV5) enters cells by fusion of the viral envelope with the plasma membrane through the concerted action of the fusion (F) protein and the receptor binding protein hemagglutinin-neuraminidase. The F protein folds initially to form a trimeric metastable prefusion form that is triggered to undergo large-scale irreversible conformational changes to form the trimeric postfusion conformation. It is thought that F refolding couples the energy released with membrane fusion. The F protein is synthesized as a precursor (F0) that must be cleaved by a host protease to form a biologically active molecule, F1,F2. Cleavage of F protein is a prerequisite for fusion and virus infectivity. Cleavage creates a new N terminus on F1 that contains a hydrophobic region, known as the FP, which intercalates target membranes during F protein refolding. The crystal structure of the soluble ectodomain of the uncleaved form of PIV5 F is known; here we report the crystal structure of the cleavage-activated prefusion form of PIV5 F. The structure shows minimal movement of the residues adjacent to the protease cleavage site. Most of the hydrophobic FP residues are buried in the uncleaved F protein, and only F103 at the newly created N terminus becomes more solvent-accessible after cleavage. The conformational freedom of the charged arginine residues that compose the protease recognition site increases on cleavage of F protein.This publication has 44 references indexed in Scilit:
- Ebola virus entry requires the cholesterol transporter Niemann–Pick C1Nature, 2011
- Structure of the Newcastle disease virus F protein in the post-fusion conformationVirology, 2010
- Structure of the Ebola virus glycoprotein bound to an antibody from a human survivorNature, 2008
- Viral membrane fusionNature Structural & Molecular Biology, 2008
- Structural basis of viral invasion: lessons from paramyxovirus FCurrent Opinion in Structural Biology, 2007
- Refolding of a paramyxovirus F protein from prefusion to postfusion conformations observed by liposome binding and electron microscopyProceedings of the National Academy of Sciences of the United States of America, 2006
- Toward the structural genomics of complexes: Crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosisProceedings of the National Academy of Sciences of the United States of America, 2006
- Structure of influenza haemagglutinin at the pH of membrane fusionNature, 1994
- Refinement of the influenza virus hemagglutinin by simulated annealingJournal of Molecular Biology, 1990
- Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolutionNature, 1981