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Download or read book Structural and Functional Insights Into the Molecular Mechanisms of Viral-cell and Cell-cell Fusion written by Halil Aydin and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Membrane fusion is an essential step in various developmental, physiological, and pathological processes in eukaryotes. Specific fusion proteins catalyze the merger of two lipid bilayers. The molecular mechanisms of many membrane fusion reactions still remain unclear. Here, we characterized the molecular details of various adhesion and fusion proteins involved in viral-cell, placental trophoblast, and sperm-egg fusion events to better understand their mechanisms. In total, nine crystal structures of these human and viral glycoproteins are presented. Furthermore, structural comparisons combined with mutagenesis, biochemical, biophysical, and cell culture experiments allowed us to investigate the implications of specific residues of these proteins in mediating membrane fusion. Structures of class I viral fusion proteins revealed that electrostatic interactions are critical for post-fusion stability in viruses that fuse at neutral pH, whereas the salt bridges do not play a stabilizing role in fusion proteins that proceed through low pH. Instead, hydrophobic residues stabilize the fusion core, and histidine/arginine residues in the chain reversal region stabilize a helix-dipole moment. Moreover, the structure of human syncytin-1 fusion protein unveiled a striking overall structural similarity to class I viral fusion proteins, and the presence of salt bridges within the fusion subunit zipper the inner and outer helices. These electrostatic interactions stabilize the post-fusion structure and provide the energetics for trophoblast cell fusion in placentation. While class I fusion proteins share similar structural and functional features, the mechanism of sperm-egg fusion requires the involvement of sperm Izumo1 and egg Juno proteins. Atomic resolution structures of Izumo1 and Juno display an interface stabilized through extensive interactions and a major conformational change within Izumo1 upon Juno binding. Moreover, mutational studies at the Izumo1-Juno interface revealed the structural determinants required for binding. We provide a comprehensive analysis that now identifies general trends and signatures important in viral-cell and cell-cell fusion events.