Mangala Prasad, V and Blijleven, JS and Smit, JM and Lee, KK (2022) Visualization of conformational changes and membrane remodeling leading to genome delivery by viral class-II fusion machinery. In: Nature Communications, 13 (1).
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Abstract
Chikungunya virus (CHIKV) is a human pathogen that delivers its genome to the host cell cytoplasm through endocytic low pH-activated membrane fusion mediated by class-II fusion proteins. Though structures of prefusion, icosahedral CHIKV are available, structural characterization of virion interaction with membranes has been limited. Here, we have used cryo-electron tomography to visualize CHIKV’s complete membrane fusion pathway, identifying key intermediary glycoprotein conformations coupled to membrane remodeling events. Using sub-tomogram averaging, we elucidate features of the low pH-exposed virion, nucleocapsid and full-length E1-glycoprotein’s post-fusion structure. Contrary to class-I fusion systems, CHIKV achieves membrane apposition by protrusion of extended E1-glycoprotein homotrimers into the target membrane. The fusion process also features a large hemifusion diaphragm that transitions to a wide pore for intact nucleocapsid delivery. Our analyses provide comprehensive ultrastructural insights into the class-II virus fusion system function and direct mechanistic characterization of the fundamental process of protein-mediated membrane fusion.
| Item Type: | Journal Article |
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| Publication: | Nature Communications |
| Publisher: | Nature Research |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | glycoprotein; virus envelope protein; virus fusion protein, chemistry; Chikungunya virus; genetics; human; membrane fusion; metabolism; virion; virus entry, Chikungunya virus; Glycoproteins; Humans; Membrane Fusion; Viral Envelope Proteins; Viral Fusion Proteins; Virion; Virus Internalization |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 17 Sep 2022 03:05 |
| Last Modified: | 17 Sep 2022 03:05 |
| URI: | https://eprints.iisc.ac.in/id/eprint/76568 |
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