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Open AccessArticle

Structural Analysis of the SANT/Myb Domain of FLASH and YARP Proteins and Their Complex with the C-Terminal Fragment of NPAT by NMR Spectroscopy and Computer Simulations

1
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, ul. Pawińskiego 5a, 02-106 Warsaw, Poland
2
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3
Integrative Program for Biological and Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
4
NanoBioMedical Centre, Adam Mickiewicz University, ul. Wszechnicy Piastowskiej 3, 61-614 Poznań, Poland
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: International Institute of Molecular and Cell Biology, ul. Ks. Trojdena 4, 02-109 Warsaw, Poland.
Int. J. Mol. Sci. 2020, 21(15), 5268; https://doi.org/10.3390/ijms21155268
Received: 26 June 2020 / Revised: 15 July 2020 / Accepted: 20 July 2020 / Published: 24 July 2020
FLICE-associated huge protein (FLASH), Yin Yang 1-Associated Protein-Related Protein (YARP) and Nuclear Protein, Ataxia-Telangiectasia Locus (NPAT) localize to discrete nuclear structures called histone locus bodies (HLBs) where they control various steps in histone gene expression. Near the C-terminus, FLASH and YARP contain a highly homologous domain that interacts with the C-terminal region of NPAT. Structural aspects of the FLASH–NPAT and YARP–NPAT complexes and their role in histone gene expression remain largely unknown. In this study, we used multidimensional NMR spectroscopy and in silico modeling to analyze the C-terminal domain in FLASH and YARP in an unbound form and in a complex with the last 31 amino acids of NPAT. Our results demonstrate that FLASH and YARP domains share the same fold of a triple α-helical bundle that resembles the DNA binding domain of Myb transcriptional factors and the SANT domain found in chromatin-modifying and remodeling complexes. The NPAT peptide contains a single α-helix that makes multiple contacts with α-helices I and III of the FLASH and YARP domains. Surprisingly, in spite of sharing a significant amino acid similarity, each domain likely binds NPAT using a unique network of interactions, yielding two distinct complexes. In silico modeling suggests that both complexes are structurally compatible with DNA binding, raising the possibility that they may function in identifying specific sequences within histone gene clusters, hence initiating the assembly of HLBs and regulating histone gene expression during cell cycle progression. View Full-Text
Keywords: Histone locus body; SANT domain; Myb DNA binding domain; NMR spectroscopy Histone locus body; SANT domain; Myb DNA binding domain; NMR spectroscopy
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Bucholc, K.; Skrajna, A.; Adamska, K.; Yang, X.-C.; Krajewski, K.; Poznański, J.; Dadlez, M.; Domiński, Z.; Zhukov, I. Structural Analysis of the SANT/Myb Domain of FLASH and YARP Proteins and Their Complex with the C-Terminal Fragment of NPAT by NMR Spectroscopy and Computer Simulations. Int. J. Mol. Sci. 2020, 21, 5268.

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