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Enzyme‐Instructed Assemblies Enable Mitochondria Localization of Histone H2B in Cancer Cells
Author(s) -
He Hongjian,
Guo Jiaqi,
Lin Xinyi,
Xu Bing
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202000983
Subject(s) - histone h2b , mitochondrion , organelle , cancer cell , microbiology and biotechnology , biochemistry , crosstalk , enzyme , biology , histone , chemistry , cancer , gene , genetics , physics , optics
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.