The role of the Mo -MuLV envelope protein in the process of membrane fusion
Abstract
Protein-mediated membrane fusion is a central process in cell biology. Studying membrane fusion has been difficult due to the complexity of the system. Fewer components are involved in the viral fusion process; therefore it is a useful model for studying membrane fusion. In this research, Moloney murine leukemia virus (Mo-MuLV), which is a retrovirus, has been used as a model for studying the process of protein-mediated membrane fusion. The viral envelope protein, which is the protein responsible for promoting fusion of the viral and cellular membranes, is structurally similar to the envelope proteins of other retroviruses, such as HIV, and unrelated viruses, such as Ebola and Influenza. It is also structurally similar to the complex of proteins involved in vesicular transport. This structural similarity suggests that these proteins may promote fusion through an analogous mechanism. The Mo-MuLV envelope protein is made up of two subunits, SU, which binds to the cellular receptor, and TM, which is responsible for promoting fusion between the viral and cellular membranes and is the focus of this research. The TM subunit has an amino-terminal fusion peptide, a membrane-spanning domain, and a cytoplasmic domain. Each of these regions was studied in detail to determine their individual function in the fusion process. Our results indicate that (1) a mutation in the hydrophobic fusion peptide plays a key role in the natural resistance to ecotropic MuLVs exhibited by some mice, (2) the membrane-spanning domain is actually forming a kinked-amphipathic alpha helix that is most likely playing a role in the formation of the aqueous fusion pore, and (3) the cytoplasmic domain of the Mo-MuLV TM subunit, which plays a role in regulating membrane fusion, also plays a role in the incorporation of the envelope protein into a budding retroviral particle. Together this research demonstrates that the different regions of the Mo-MuLV TM subunit are involved in different steps of the fusion process. The fusion peptide and membrane-spanning domains are absolutely necessary for fusion, whereas the cytoplasmic domain is necessary for both the regulation of fusion and for incorporating the envelope protein into a virus particle.
Degree
Ph.D.
Advisors
Sanders, Purdue University.
Subject Area
Cellular biology|Molecular biology
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