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Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability
- Source :
- Journal of Biological Chemistry
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains implicated the TM domain in the fusion process, but the structural and molecular details in fusion remain unclear. Previously, analytical ultracentrifugation was utilized to demonstrate that isolated TM domains of Hendra virus F protein associate in a monomer-trimer equilibrium (Smith, E. C., Smith, S. E., Carter, J. R., Webb, S. R., Gibson, K. M., Hellman, L. M., Fried, M. G., and Dutch, R. E. (2013) J. Biol. Chem. 288, 35726–35735). To determine factors driving this association, 140 paramyxovirus F protein TM domain sequences were analyzed. A heptad repeat of β-branched residues was found, and analysis of the Hendra virus F TM domain revealed a heptad repeat leucine-isoleucine zipper motif (LIZ). Replacement of the LIZ with alanine resulted in dramatically reduced TM-TM association. Mutation of the LIZ in the whole protein resulted in decreased protein stability, including pre-fusion conformation stability. Together, our data suggest that the heptad repeat LIZ contributed to TM-TM association and is important for F protein function and pre-fusion stability.
- Subjects :
- 0301 basic medicine
Amino Acid Motifs
Mutation, Missense
Biology
Biochemistry
Hendra Virus
Cell membrane
Structure-Activity Relationship
03 medical and health sciences
Protein Domains
Viral envelope
Chlorocebus aethiops
medicine
Animals
Molecular Biology
030102 biochemistry & molecular biology
Viral Core Proteins
Lipid bilayer fusion
Cell Biology
Fusion protein
Transmembrane protein
Cell biology
Transmembrane domain
Heptad repeat
030104 developmental biology
medicine.anatomical_structure
Amino Acid Substitution
Protein Structure and Folding
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 292
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....b592d29418439c326d719c1d08a1406f
- Full Text :
- https://doi.org/10.1074/jbc.m117.777235