Enzyme-Instructed Assemblies Enable Mitochondria Localization of Histone H2B in Cancer Cells |
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Authors: | Hongjian He Jiaqi Guo Xinyi Lin Prof. Dr. Bing Xu |
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Affiliation: | Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA, 02453 USA |
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Abstract: | Presently, little is known of how the inter-organelle crosstalk impacts cancer cells owing to the lack of approaches that can manipulate inter-organelle communication in cancer cells. We found that a negatively charged, enzyme cleavable peptide (MitoFlag) enables the trafficking of histone protein H2B, a nuclear protein, to the mitochondria in cancer cells. MitoFlag interacts with the nuclear location sequence of H2B to block it from entering the nucleus. A protease on the mitochondria cleaves the Flag from the MitoFlag/H2B complex to form assemblies that retain H2B on the mitochondria and facilitate H2B entering the mitochondria. Adding NLS, replacing aspartic acid by glutamic acid residues, or changing the l - to d -aspartic acid residue on MitoFlag abolishes the trafficking of H2B into mitochondria of HeLa cells. As the first example of the enzyme-instructed self-assembly of a synthetic peptide for trafficking endogenous proteins, this work provides insights for understanding and manipulating inter-organelle communication in cells. |
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Keywords: | enzymes histone H2B mitochondria peptides self-assembly |
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