期刊
NUCLEIC ACIDS RESEARCH
卷 37, 期 20, 页码 6765-6783出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkp750
关键词
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资金
- The European Union FP6 Proteomage
- MRC Career Development Fellowship
- MRC [MC_U105192716] Funding Source: UKRI
- Medical Research Council [MC_U105192716] Funding Source: researchfish
Human mitochondrial transcription factor A (TFAM) is a multi-functional protein, involved in different aspects of maintaining mitochondrial genome integrity. In this report, we characterized TFAM and its interaction with tumor suppressor p53 using various biophysical methods. DNA-free TFAM is a thermally unstable protein that is in equilibrium between monomers and dimers. Self-association of TFAM is modulated by its basic C-terminal tail. The DNA-binding ability of TFAM is mainly contributed by its first HMG-box, while the second HMG-box has low-DNA-binding capability. We also obtained backbone resonance assignments from the NMR spectra of both HMG-boxes of TFAM. TFAM binds primarily to the N-terminal transactivation domain of p53, with a K-d of 1.95 +/- 0.19 mu M. The C-terminal regulatory domain of p53 provides a secondary binding site for TFAM. The TFAM-p53-binding interface involves both TAD1 and TAD2 sub-domains of p53. Helices alpha 1 and alpha 2 of the HMG-box constitute the main p53-binding region. Since both TFAM and p53 binds preferentially to distorted DNA, the TFAM-p53 interaction is implicated in DNA damage and repair. In addition, the DNA-binding mechanism of TFAM and biological relevance of the TFAM-p53 interaction are discussed.
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