The DNA Binding and Bending Activities of Truncated Tail-less HMGB1 protein are Differentially Affected by Lys-2 and Lys-81 Residues and Their Acetylation

Elenkov, Ivan; Pelovsky, Petar; Ugrinova, Iva; Takahashi, Masayuki; Pasheva, Evdokia

doi:10.7150/ijbs.7.691

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Int J Biol Sci 2011; 7(6):691-699. doi:10.7150/ijbs.7.691 This issue Cite

Research Paper

The DNA Binding and Bending Activities of Truncated Tail-less HMGB1 protein are Differentially Affected by Lys-2 and Lys-81 Residues and Their Acetylation

Ivan Elenkov¹, Petar Pelovsky¹, Iva Ugrinova¹, Masayuki Takahashi², Evdokia Pasheva^{1 ✉}

1. Institute of Moleculat Biology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
2. UMR 6204 CNRS, Université de Nantes, Nantes, France

Citation:

Elenkov I, Pelovsky P, Ugrinova I, Takahashi M, Pasheva E. The DNA Binding and Bending Activities of Truncated Tail-less HMGB1 protein are Differentially Affected by Lys-2 and Lys-81 Residues and Their Acetylation. Int J Biol Sci 2011; 7(6):691-699. doi:10.7150/ijbs.7.691. https://www.ijbs.com/v07p0691.htm

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Abstract

The role of lysines 2 and 81 as target sites for acetylation in full-length HMGB1 and truncated tail-less protein, respectively, has been studied by mutation analysis for the abilities of these proteins to bind and bend DNA. The DNA bending ability of truncated tail-less HMGB1 containing Lys-2 mutated to alanine does not differ from that of the wild-type protein, while the same mutation of Lys-81 reduced the bending capacity of the mutant protein. These data demonstrate that Lys-81 is critical for the DNA bending ability of truncated HMGB1. Such a conclusion is further confirmed by the experiments carried out with CBP-acetylated proteins: acetylation of Lys-2 in mutant protein K81/A81 alleviated DNA bending and induced DNA end-joining. On the contrary, the acetylation of Lys-81 in the mutant K2/A2 enhanced the bending potential of HMGB1∆C. Regarding the ability of HMGB1 to specifically bind bent DNA, the individual mutations of either K2 or K81 as well as the double mutation of both residues to alanine were found to completely abolish binding of truncated tail-less HMGB1 to cisplatin-modified DNA. We conclude that unlike the case with the bending ability of truncated HMGB1, where Lys-81 has a primary function, Lys-2 and Lys-81 are both critical for the protein's binding to cisplatin-modified DNA. The mutation K2/A2 in full-length HMGB1 and acidic tail removal induce the same conformational changes. Any further substitutions at the acetylable lysines in the truncated form of HMGB1 do not have an additional effect.

Keywords: HMGB1 protein, tail-less HMGB1 protein, Lys-2 and Lys-81 residues, acetylation, binding to platinated DNA, DNA bending.

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APA

Elenkov, I., Pelovsky, P., Ugrinova, I., Takahashi, M., Pasheva, E. (2011). The DNA Binding and Bending Activities of Truncated Tail-less HMGB1 protein are Differentially Affected by Lys-2 and Lys-81 Residues and Their Acetylation. International Journal of Biological Sciences, 7(6), 691-699. https://doi.org/10.7150/ijbs.7.691.

ACS

Elenkov, I.; Pelovsky, P.; Ugrinova, I.; Takahashi, M.; Pasheva, E. The DNA Binding and Bending Activities of Truncated Tail-less HMGB1 protein are Differentially Affected by Lys-2 and Lys-81 Residues and Their Acetylation. Int. J. Biol. Sci. 2011, 7 (6), 691-699. DOI: 10.7150/ijbs.7.691.

NLM

CSE

Elenkov I, Pelovsky P, Ugrinova I, Takahashi M, Pasheva E. 2011. The DNA Binding and Bending Activities of Truncated Tail-less HMGB1 protein are Differentially Affected by Lys-2 and Lys-81 Residues and Their Acetylation. Int J Biol Sci. 7(6):691-699.

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