The HA (haemagglutinin) of influenza viruses must be recruited to membrane rafts to perform its function in membrane fusion and virus budding. We previously showed using FRET that deletion of the two raft-targeting features of HA, S-acylation at the cytoplasmic tail and the hydrophobic amino acids VIL (Val-Ile-Leu) in the outer part of the TMR (transmembrane region), lead to reduced raft association. In addition, exchange of VIL, but not of the S-acylation sites severely retards transport of HA through the Golgi. In the present study, we have further characterized the ill-defined signal in the TMR. A sequence comparison suggests that the leucine residue of VIL might be part of a CCM (cholesterol consensus motif) that is known to bind cholesterol to seven-transmembrane receptors. The signal also comprises a lysine residue and a tryptophan residue on one and a tyrosine residue on another TMR helix and is conserved in group 2 HAs. Mutations in the CCM retard Golgi-localized processing of HA, such as acquisition of Endo H (endoglycosidase H)-resistant carbohydrates in the medial Golgi and proteolytic cleavage in the TGN (trans-Golgi network). The delay in transport of HA to and from the medial Golgi varied with the mutation, suggesting that different transport steps are affected. All mutants analysed by FRET also showed reduced association with rafts at the plasma membrane. Thus the raft-targeting signal of HA encompasses not only hydrophobic, but also aromatic and positively charged, residues. We speculate that binding to cholesterol might facilitate intracellular transport of HA and association with rafts.
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Research Article|
January 06 2015
A cholesterol consensus motif is required for efficient intracellular transport and raft association of a group 2 HA from influenza virus
Maren de Vries;
Maren de Vries
*Institute of Virology, Veterinary Faculty, Free University Berlin, Robert-von-Ostertag-Straße 7-13, 14163 Berlin, Germany
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Andreas Herrmann;
Andreas Herrmann
†Department of Biology, Molecular Biophysics, Humboldt University Berlin, Invalidenstraße 42, 10115 Berlin, Germany
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Michael Veit
Michael Veit
1
*Institute of Virology, Veterinary Faculty, Free University Berlin, Robert-von-Ostertag-Straße 7-13, 14163 Berlin, Germany
1To whom correspondence should be addressed (email mveit@zedat.fu-berlin.de).
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Publisher: Portland Press Ltd
Received:
September 01 2014
Revision Received:
October 15 2014
Accepted:
October 21 2014
Accepted Manuscript online:
October 21 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2015 Biochemical Society
2015
Biochem J (2015) 465 (2): 305–314.
Article history
Received:
September 01 2014
Revision Received:
October 15 2014
Accepted:
October 21 2014
Accepted Manuscript online:
October 21 2014
Citation
Maren de Vries, Andreas Herrmann, Michael Veit; A cholesterol consensus motif is required for efficient intracellular transport and raft association of a group 2 HA from influenza virus. Biochem J 15 January 2015; 465 (2): 305–314. doi: https://doi.org/10.1042/BJ20141114
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