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Phosphorylation in the accessory domain of yeast histone chaperone protein 1 exposes the nuclear export signal sequence
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  • Sho Ashida,
  • Rikuri Morita,
  • Yasuteru Shigeta,
  • Ryuhei Harada
Sho Ashida
University of Tsukuba
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Rikuri Morita
University of Tsukuba
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Yasuteru Shigeta
University of Tsukuba
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Ryuhei Harada
University of Tsukuba
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Abstract

Histone is a scaffold protein that constitutes nucleosomes with DNA in the cell nucleus. When forming histone, hetero octamer is assisted by histone chaperone proteins. As a histone chaperone protein, the crystal structure of yeast nucleosome assembly protein (yNap1) has been determined. For yNap1, a nuclear export signal/sequence (NES) has been identified as a part of the long -helix. Experimental evidence via mutagenesis on budding yeast suggests the NES is necessary for transport out from the cell nucleus. However, the NES is masked by a region defined as an accessory domain (AD). In addition, the role of the AD in nuclear transport has not been elucidated yet. To address the role of the AD, we focused on phosphorylation in the AD because proteome experiments have identified multiple phosphorylation sites of yNap1. To computationally treat phosphorylation, we performed all-atom molecular dynamics (MD) simulations for a set of non-phosphorylated and phosphorylated yNap1 (Nap1-nonP and Nap1-P). As an analysis, we addressed how the NES is exposed to the protein surface by measuring its solvent-access surface area (SASA). As a result, there was a difference in the SASA distributions between both systems. Quantitatively, the median of the SASA distribution of Nap1-P was greater than that of Nap1-nonP, meaning that phosphorylation in the AD exposed to the NES, resulting in increasing its accessibility. In conclusion, yNap1 might modulate the accessibility of the NES by dislocating the AD through phosphorylation.

Peer review status:IN REVISION

04 Mar 2021Submitted to PROTEINS: Structure, Function, and Bioinformatics
04 Mar 2021Submission Checks Completed
04 Mar 2021Assigned to Editor
11 Mar 2021Reviewer(s) Assigned
17 Jun 2021Review(s) Completed, Editorial Evaluation Pending
17 Jun 2021Editorial Decision: Revise Minor
01 Jul 20211st Revision Received
16 Jul 2021Assigned to Editor
16 Jul 2021Submission Checks Completed