Ebolavirus Entry Requires a Compact Hydrophobic Fist at the Tip of the Fusion Loop
| Autor: | Elizabeth A. Nelson, Sonia M. Gregory, Lukas K. Tamm, Peter M. Kasson, Per Larsson, Judith M. White |
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| Rok vydání: | 2014 |
| Předmět: |
Viral protein
Endosome Molecular Sequence Data Immunology Molecular Dynamics Simulation Biology medicine.disease_cause Microbiology Cell Line Viral Envelope Proteins Viral envelope Viral entry Virology medicine Humans Amino Acid Sequence Ebolavirus Fusion Lipid bilayer fusion Hemorrhagic Fever Ebola Virus Internalization Fusion protein Virus-Cell Interactions Biochemistry Insect Science Biophysics Hydrophobic and Hydrophilic Interactions |
| Zdroj: | Journal of Virology. 88:6636-6649 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | Ebolavirus is an enveloped virus causing severe hemorrhagic fever. Its surface glycoproteins undergo proteolytic cleavage and rearrangements to permit membrane fusion and cell entry. Here we focus on the glycoprotein's internal fusion loop (FL), critical for low-pH-triggered fusion in the endosome. Alanine mutations at L529 and I544 and particularly the L529 I544 double mutation compromised viral entry and fusion. The nuclear magnetic resonance (NMR) structures of the I544A and L529A I544A mutants in lipid environments showed significant disruption of a three-residue scaffold that is required for the formation of a consolidated fusogenic hydrophobic surface at the tip of the FL. Biophysical experiments and molecular simulation revealed the position of the wild-type (WT) FL in membranes and showed the inability of the inactive double mutant to reach this position. Consolidation of hydrophobic residues at the tip of FLs may be a common requirement for internal FLs of class I, II, and III fusion proteins. IMPORTANCE Many class I, II, and III viral fusion proteins bear fusion loops for target membrane insertion and fusion. We determined structures of the Ebolavirus fusion loop and found residues critical for forming a consolidated hydrophobic surface, membrane insertion, and viral entry. |
| Databáze: | OpenAIRE |
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