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pH Might play a role in regulating the function of paired amphipathic helices domains of human Sin3B by altering structure and thermodynamic stability

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Abstract

Human Sin3B (hSin3B), a transcription regulator, is a scaffold protein that binds to different transcription factors and regulates transcription. It consists of six conserved domains that include four paired amphipathic helices (PAH 1–4), histone deacetylase interaction domain (HID), and highly conserved region (HCR). Interestingly, the PAH domains of hSin3B are significantly homologous to each other, yet each one interacts with a specific set of unique transcription factors. Though various partners interacting with hSin3B PAH domains have been characterized, there is no structural information available on the individual PAH domains of hSin3B. Here we characterize the structure and stability of different PAH domains of hSin3B at both nuclear and physiological pH values by using different optical probes. We found that the native state structure and stability of different PAH domains are different at nuclear pH where hSin3B performs its biological function. We also found that PAH2 and PAH3 behave differently at both nuclear and physiological pH in terms of native state structure and thermodynamic stability, while the structural identity of PAH1 remains unaltered at both pH values. The study indicates that the structural heterogeneity of different PAH domains might be responsible for having a unique set of interacting transcription factors.

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Abbreviations

HCR:

highly conserved region

HID:

histone deacetylase interaction domain

PAH:

paired amphipathic helices domain

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Authors and Affiliations

  1. Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110-007, India

    Tauheed Hasan, Mashook Ali, Daman Saluja & Laishram Rajendrakumar Singh

Authors
  1. Tauheed Hasan
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  2. Mashook Ali
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  3. Daman Saluja
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  4. Laishram Rajendrakumar Singh
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Corresponding author

Correspondence to Laishram Rajendrakumar Singh.

Additional information

Published in Russian in Biokhimiya, 2015, Vol. 80, No. 4, pp. 497–507.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM14-235, February 15, 2015.

These authors contributed equally to this work.

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Hasan, T., Ali, M., Saluja, D. et al. pH Might play a role in regulating the function of paired amphipathic helices domains of human Sin3B by altering structure and thermodynamic stability. Biochemistry Moscow 80, 424–432 (2015). https://doi.org/10.1134/S0006297915040057

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  • DOI: https://doi.org/10.1134/S0006297915040057

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