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Conserved C-terminal nascent peptide binding domain of HYPK facilitates its chaperone-like activity

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Abstract

Human HYPK (Huntingtin Yeast-two-hybrid Protein K) is an intrinsically unstructured chaperone-like protein with no sequence homology to known chaperones. HYPK is also known to be a part of ribosome-associated protein complex and present in polysomes. The objective of the present study was to investigate the evolutionary influence on HYPK primary structure and its impact on the protein’s function. Amino acid sequence analysis revealed 105 orthologs of human HYPK from plants, lower invertebrates to mammals. C-terminal part of HYPK was found to be particularly conserved and to contain nascent polypeptide-associated alpha subunit (NPAA) domain. This region experiences highest selection pressure, signifying its importance in the structural and functional evolution. NPAA domain of human HYPK has unique amino acid composition preferring glutamic acid and happens to be more stable from a conformational point of view having higher content of α-helices than the rest. Cell biology studies indicate that overexpressed C-terminal human HYPK can interact with nascent proteins, co-localizes with huntingtin, increases cell viability and decreases caspase activities in Huntington’s disease (HD) cell culture model. This domain is found to be required for the chaperone-like activity of HYPK in vivo. Our study suggested that by virtue of its flexibility and nascent peptide binding activity, HYPK may play an important role in assisting protein (re)folding.

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Acknowledgements

We acknowledge the computational facility of DIC and Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta. SR is supported by the DBT–Ramalingaswami Fellowship.

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Authors and Affiliations

  1. Crystallography and Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata, 700 064, India

    Swasti Raychaudhuri & Nitai P Bhattacharyya

  2. CSIR–Centre for Cellular and Molecular Biology, Hyderabad, 500 007, India

    Swasti Raychaudhuri

  3. Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, Kolkata, 700 009, India

    Rachana Banerjee & Subhasish Mukhopadhyay

Authors
  1. Swasti Raychaudhuri
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  2. Rachana Banerjee
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  3. Subhasish Mukhopadhyay
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  4. Nitai P Bhattacharyya
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Corresponding authors

Correspondence to Swasti Raychaudhuri or Nitai P Bhattacharyya.

Additional information

Corresponding editor: Veena K Parnaik

[Raychaudhuri S, Banerjee R, Mukhopadhyay S and Bhattacharyya NP 2014 Conserved C-terminal nascent peptide binding domain of HYPK facilitates its chaperone-like activity. J. Biosci. 39 1–14] DOI 10.1007/s12038-014-9442-z

Supplementary materials pertaining to this article are available on the Journal of Biosciences Website at http://www.ias.ac.in/jbiosci/sep2014/supp/Raychaudhuri.pdf

Swasti Raychaudhuri and Rachana Banerjee contributed equally to this work.

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Raychaudhuri, S., Banerjee, R., Mukhopadhyay, S. et al. Conserved C-terminal nascent peptide binding domain of HYPK facilitates its chaperone-like activity. J Biosci 39, 659–672 (2014). https://doi.org/10.1007/s12038-014-9442-z

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  • DOI: https://doi.org/10.1007/s12038-014-9442-z

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