2.50
Hdl Handle:
http://hdl.handle.net/10033/613859
Title:
The histone chaperone sNASP binds a conserved peptide motif within the globular core of histone H3 through its TPR repeats.
Authors:
Bowman, Andrew; Lercher, Lukas; Singh, Hari R; Zinne, Daria; Timinszky, Gyula; Carlomagno, Teresa ( 0000-0002-2437-2760 ) ; Ladurner, Andreas G
Abstract:
Eukaryotic chromatin is a complex yet dynamic structure, which is regulated in part by the assembly and disassembly of nucleosomes. Key to this process is a group of proteins termed histone chaperones that guide the thermodynamic assembly of nucleosomes by interacting with soluble histones. Here we investigate the interaction between the histone chaperone sNASP and its histone H3 substrate. We find that sNASP binds with nanomolar affinity to a conserved heptapeptide motif in the globular domain of H3, close to the C-terminus. Through functional analysis of sNASP homologues we identified point mutations in surface residues within the TPR domain of sNASP that disrupt H3 peptide interaction, but do not completely disrupt binding to full length H3 in cells, suggesting that sNASP interacts with H3 through additional contacts. Furthermore, chemical shift perturbations from(1)H-(15)N HSQC experiments show that H3 peptide binding maps to the helical groove formed by the stacked TPR motifs of sNASP. Our findings reveal a new mode of interaction between a TPR repeat domain and an evolutionarily conserved peptide motif found in canonical H3 and in all histone H3 variants, including CenpA and have implications for the mechanism of histone chaperoning within the cell.
Affiliation:
Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universit ̈ at München, Großhaderner Strasse 9..
Citation:
The histone chaperone sNASP binds a conserved peptide motif within the globular core of histone H3 through its TPR repeats. 2016, 44 (7):3105-17 Nucleic Acids Res.
Journal:
Nucleic acids research
Issue Date:
20-Apr-2016
URI:
http://hdl.handle.net/10033/613859
DOI:
10.1093/nar/gkv1372
PubMed ID:
26673727
Type:
Article
Language:
en
ISSN:
1362-4962
Appears in Collections:
Publications of the working group NMR-based structural chemistry (NBSC)

Full metadata record

DC FieldValue Language
dc.contributor.authorBowman, Andrewen
dc.contributor.authorLercher, Lukasen
dc.contributor.authorSingh, Hari Ren
dc.contributor.authorZinne, Dariaen
dc.contributor.authorTiminszky, Gyulaen
dc.contributor.authorCarlomagno, Teresaen
dc.contributor.authorLadurner, Andreas Gen
dc.date.accessioned2016-06-21T09:28:36Zen
dc.date.available2016-06-21T09:28:36Zen
dc.date.issued2016-04-20en
dc.identifier.citationThe histone chaperone sNASP binds a conserved peptide motif within the globular core of histone H3 through its TPR repeats. 2016, 44 (7):3105-17 Nucleic Acids Res.en
dc.identifier.issn1362-4962en
dc.identifier.pmid26673727en
dc.identifier.doi10.1093/nar/gkv1372en
dc.identifier.urihttp://hdl.handle.net/10033/613859en
dc.description.abstractEukaryotic chromatin is a complex yet dynamic structure, which is regulated in part by the assembly and disassembly of nucleosomes. Key to this process is a group of proteins termed histone chaperones that guide the thermodynamic assembly of nucleosomes by interacting with soluble histones. Here we investigate the interaction between the histone chaperone sNASP and its histone H3 substrate. We find that sNASP binds with nanomolar affinity to a conserved heptapeptide motif in the globular domain of H3, close to the C-terminus. Through functional analysis of sNASP homologues we identified point mutations in surface residues within the TPR domain of sNASP that disrupt H3 peptide interaction, but do not completely disrupt binding to full length H3 in cells, suggesting that sNASP interacts with H3 through additional contacts. Furthermore, chemical shift perturbations from(1)H-(15)N HSQC experiments show that H3 peptide binding maps to the helical groove formed by the stacked TPR motifs of sNASP. Our findings reveal a new mode of interaction between a TPR repeat domain and an evolutionarily conserved peptide motif found in canonical H3 and in all histone H3 variants, including CenpA and have implications for the mechanism of histone chaperoning within the cell.en
dc.language.isoenen
dc.titleThe histone chaperone sNASP binds a conserved peptide motif within the globular core of histone H3 through its TPR repeats.en
dc.typeArticleen
dc.contributor.departmentBiomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universit ̈ at München, Großhaderner Strasse 9..en
dc.identifier.journalNucleic acids researchen

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