期刊
STRUCTURE
卷 17, 期 5, 页码 670-679出版社
CELL PRESS
DOI: 10.1016/j.str.2009.02.017
关键词
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资金
- NCI NIH HHS [CA87658, R01 CA087658] Funding Source: Medline
- NHGRI NIH HHS [R01 HG004508-02, R01 HG004508] Funding Source: Medline
- NIGMS NIH HHS [R01 GM073207-04, R01 GM073207, GM73207] Funding Source: Medline
Human autoimmune regulator (AIRE) functions to control thymic expression of tissue-specific antigens via sequence-specific histone H3 recognition by its plant homeodomain (PHD) finger. Mutations in the AIRE PHD finger have been linked to autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Here we report the three-dimensional solution structure of the first PHD finger of human AIRE bound to a histone H3 peptide. The structure reveals a detailed network of interactions between the protein and the amino-terminal residues of histone H3, and particularly key electrostatic interactions of a conserved aspartic acid 297 in AIRE with the unmodified lysine 4 of histone H3 (H3K4). NMR binding study with H3 peptides carrying known post-translational modifications flanking H3K4 confirms that transcriptional regulation by AIRE through its interactions with histone H3 is confined to the first N-terminal eight residues in H3. Our study offers a molecular explanation for the APECED mutations and helps define a subclass of the PHD finger family proteins that recognize histone H3 in a sequence-specific manner.
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