Conserved C-terminal nascent peptide binding domain of HYPK facilitates its chaperone-like activity.
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Date
2014-09
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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.
Description
Keywords
Chaperones, evolution, HYPK, nascent peptide binding domain, orthologs, selection pressure
Citation
Raychaudhuri Swasti, Banerjee Rachana, Mukhopadhyay Subhasish, Bhattacharyya Nitai P. Conserved C-terminal nascent peptide binding domain of HYPK facilitates its chaperone-like activity. Journal of Biosciences. 2014 Sep; 39 (4): 659-672.