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16.9: Mitochondrial Precursor Proteins

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Cell Biology

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Mitochondrial Precursor Proteins

16.9: Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.

Most of the mitochondrial precursors recognized by TOM20 carry cleavable alpha-helical amphipathic presequences, whereas precursors recognized by TOM70 receptors have non-cleavable internal import signals. Similar to the presequences of mitochondrial precursors, ER precursors also carry alpha-helical signal sequences. TOM20 recognizes the mitochondrial precursor by interacting with three leucine residues, characteristic of a mitochondrial presequence. In addition, a shallow binding groove of TOM20 allows it to accommodate only amphipathic alpha-helices while avoiding the hydrophobic alpha-helices of ER precursors.

Presequences have no consensus motif; however, the nature of the amino acid residues determines the fidelity of the recognition process. Presequences such as the matrix targetting sequences have hydrophobic residues on one side of the helix and hydrophilic residues lining the other. During translocation, these hydrophobic residues interact with non-polar acyl chains of the bilayer core. In contrast, the hydrophilic residues on the other side of the presequence participate in electrostatic interactions with the polar phosphate heads of the lipid bilayer. Additionally, the hydrophilic positively charged residues on the presequences also enhance the precursor’s affinity towards negative charges on the matrix side of the inner membrane, thereby providing it the necessary energy required to cross the lipid bilayer and initiate the translocation process.

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