A fusion complex is protein machinery merging biological membranes. These complexes join two lipid bilayers, the fundamental barriers of cells and their compartments. This intricate process is a fundamental requirement for many life processes, enabling cell function and interaction.
How Cells Fuse Membranes
Merging two biological membranes presents challenges due to repulsion between negatively charged surfaces. The lipid bilayers are also stable, requiring energy to overcome resistance to deformation. Fusion complexes address these barriers by orchestrating precise steps for membrane merger.
The process begins with recognition and adhesion, where proteins on membrane surfaces bind, bringing membranes into close proximity. Membrane surface dehydration follows, removing water molecules that act as a barrier to lipid interaction. Next, fusion proteins undergo conformational changes, often described as a “zippering” action, pulling membranes closer.
This pulling action leads to the formation of a hemifusion stalk, an intermediate structure where only outer leaflets merge. Lipids from outer leaflets mix, creating a connection. The stalk then expands, allowing inner leaflets to contact.
Finally, inner leaflets also merge, forming a fusion pore. This small opening allows contents of separate compartments to mix. The pore expands, completing fusion and creating a continuous membrane. Fusion proteins act as catalysts, lowering energy barriers at each stage, ensuring this sequence occurs efficiently and at the correct time and location.
Vital Functions in the Body
Fusion complexes are important for physiological processes like communication, transport, and development. In the nervous system, they are central to neurotransmission, or nerve cell communication. SNARE proteins mediate synaptic vesicle fusion with the presynaptic membrane, releasing neurotransmitters. When a nerve impulse arrives and calcium enters the synapse, it binds to proteins like synaptotagmin, triggering SNARE proteins to pull the vesicle and plasma membranes together, releasing them into the synaptic cleft.
Fusion complexes also play a role in viral entry into host cells, exploited by many enveloped viruses like influenza, Ebola, and HIV. These viruses have envelope fusion proteins that bind to host cell receptors. For example, HIV’s gp41 protein undergoes a conformational change after binding to CD4 and co-receptors, leading to fusion of viral and host cell membranes, allowing genetic material to enter.
Fusion complexes also facilitate cell-cell fusion. This is important in fertilization, where sperm and egg membranes fuse. During development, cell-cell fusion forms multinucleated structures like skeletal muscle fibers, where myoblasts merge to form muscle cells.
Within cells, fusion complexes are active in intracellular vesicle trafficking, ensuring material transport between organelles. For instance, proteins from the endoplasmic reticulum are packaged into vesicles that fuse with the Golgi apparatus for modification and sorting. Lysosomes, containing digestive enzymes, fuse with phagosomes holding engulfed waste or pathogens to break down materials, maintaining cellular cleanup and defense.
Implications for Disease and Medicine
Malfunctions in fusion complexes can have consequences, contributing to disease. Defects in proteins governing intracellular membrane fusion link to neurodegenerative, mitochondrial, and lysosomal storage diseases. For instance, if SNARE proteins, involved in neurotransmission, do not function correctly, neurotransmitter release can be impaired, leading to neurological dysfunction.
Many viral infections, including coronaviruses like SARS-CoV-2, rely on viral fusion proteins to enter host cells. The SARS-CoV-2 spike protein, for example, undergoes conformational changes facilitating fusion of its envelope with the host cell membrane. This dependence makes these proteins attractive targets for antiviral therapies.
Understanding how fusion complexes work has opened therapeutic avenues. For viral infections, drugs can block viral fusion, preventing entry. For example, some antiviral peptides mimic parts of viral fusion proteins, interfering with conformational changes necessary for fusion, inhibiting infection (an approach used against HIV and explored for SARS-CoV-2). Researchers are also exploring strategies to enhance membrane repair, involving vesicle-vesicle fusion to patch damaged plasma membranes. This could offer new treatments for neurodegenerative conditions with compromised membrane integrity.