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The fusion protein core of measles virus forms stable coiled-coil trimer
Jieqing Zhu1, Catherine W-H Zhang, Yipeng Qi
1Department of Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Zhongguancun Beiyitiao, Beijing 100080, China.
Abstract:
Recent studies have shown that paramyxovirus might adopt a similar molecular mechanism of virus entry and fusion in which the attachment glycoprotein binds receptor/s and triggers the conformational changes of the fusion protein. There are two conserved regions of heptad repeat (HR1 and HR2) in the fusion protein and they were shown with fusion-inhibition effects in many paramyxoviruses, including measles virus. They also appear to show characteristic structure in the fusion core: the HR1/HR2 forms stable six-helix coiled-coil centered by HR1 and is surrounded by HR2 (trimer of HR1/HR2), which represents the post-fusion conformational structure. In this study, we expressed the HR1 and HR2 of measles virus fusion protein as a single chain (named 2-Helix) and subsequently tested its formation of trimer. Indeed, the results do show that the HR1 and HR2 interact with each other and form stable six-helix coiled-coil bundle. This is the first member in genus Morbillivirus of family Paramyxoviridae to be confirmed with this characteristic structure and provides the basis for the HR2-inhibition effects on virus fusion/entry for measles virus.
Insights
Measles virus fusion protein’s heptad repeat regions (HR1 and HR2) form a stable six-helix bundle. This structure confirms HR2
Area of Science:
- Virology
- Molecular Biology
- Structural Biology
Background:
- Paramyxoviruses utilize a conserved mechanism for viral entry and fusion.
- The fusion protein's heptad repeat regions (HR1 and HR2) are critical for this process and exhibit fusion-inhibitory effects.
- A characteristic post-fusion structure involves a six-helix coiled-coil bundle formed by HR1 and HR2.
Purpose of the Study:
- To investigate the formation of the six-helix coiled-coil bundle in the measles virus fusion protein.
- To confirm the interaction between HR1 and HR2 domains in measles virus.
- To provide a structural basis for HR2-mediated inhibition of measles virus entry.
Main Methods:
- Expression of a single-chain construct containing HR1 and HR2 domains of the measles virus fusion protein (termed 2-Helix).
- Analysis of the self-assembly and structural properties of the expressed 2-Helix construct.
Main Results:
- The expressed 2-Helix construct successfully formed a stable six-helix coiled-coil bundle.
- Demonstrated direct interaction between the HR1 and HR2 regions of the measles virus fusion protein.
- This is the first confirmation of this characteristic structure in a member of the Morbillivirus genus.
Conclusions:
- The HR1 and HR2 domains of the measles virus fusion protein assemble into a stable six-helix coiled-coil bundle, representing the post-fusion conformation.
- This structural confirmation supports the role of HR2 in inhibiting measles virus fusion and entry.
- Establishes a structural foundation for developing antiviral strategies targeting measles virus entry.