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Kanazawa, Japan, July 14, 2021 /PRNewswire/ – Kanazawa University researchers at Proceedings of the National Academy of Sciences How does a protein molecular motor cut a piece of cell membrane. The contraction and cutting mechanism is similar to a ratchet motor and is important in mediating particles into the cell.
Cells in the human body continuously receive substances from the outside through a process called endocytosis. An important endocytosis pathway involves the formation of protrusions in the cell membrane that point to the inside of the cell, which is triggered when molecules that need to enter reach the membrane. The protrusion wraps and closes the molecule, then cuts it off, leaving the wrapped molecule (the so-called vesicle) inside the cell. Dynein plays a key role in the severing mechanism. Dynein is a protein that locally “shrinks” the cell membrane and sever the fragments. However, the precise contraction mechanism is not fully understood. Now, by combining experiments and simulations that explore the dynamics of dynein, Alexander Mikhailov Research from Kanazawa University and colleagues showed that the working principle of this “nano muscle” is similar to that of a ratchet motor.
Dynamin consists of spiral filaments that are coiled around the neck of a vesicle formed in the membrane. In the presence of GTP (a molecule that can be considered a biochemical “fuel” because it provides energy), these filaments begin to slide, thus shrinking the neck of the vesicle. To understand the mechanism of contraction in detail, Mikhailov and colleagues used a technique called single-molecule fluorescence resonance energy transfer (smFRET), which measures the distance in biomolecules. The data obtained show that different conformations of dynein filaments occur, depending on whether they bind to GTP and its products. These different configurations result in the formation of molecular “bridges” of different orientations between adjacent coil turns. Supply GTP and hydrolyze…
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