Structural and histone binding ability characterizations of human PWWP domains

Hong Wu, Hong Zeng, Robert Lam, Wolfram Tempel, Maria F. Amaya, Chao Xu, Ludmila Dombrovski, Wei Qiu, Yanming Wang, Jinrong Min

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Background: The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. Methodology/Principal Findings: The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. Conclusions: PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical β-barrel core, an insertion motif between the second and third β-strands and a C-terminal α-helix bundle. Both the canonical β-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones. Enhanced version: This article can also be viewed as an (http://www.plosone.org/enhanced/pone.0018919) in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

Original languageEnglish (US)
Article numbere18919
JournalPloS one
Volume6
Issue number6
DOIs
StatePublished - Jun 28 2011

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Aptitude
binding capacity
histones
Histones
DNA-binding domains
crystal structure
DNA
Proteins
proteins
Crystal structure
Protein Interaction Domains and Motifs
Fluorescence Polarization
new family
protein-protein interactions
titration
Titration
Lysine
Binders
Sequence Analysis
lysine

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Wu, H., Zeng, H., Lam, R., Tempel, W., Amaya, M. F., Xu, C., ... Min, J. (2011). Structural and histone binding ability characterizations of human PWWP domains. PloS one, 6(6), [e18919]. https://doi.org/10.1371/journal.pone.0018919
Wu, Hong ; Zeng, Hong ; Lam, Robert ; Tempel, Wolfram ; Amaya, Maria F. ; Xu, Chao ; Dombrovski, Ludmila ; Qiu, Wei ; Wang, Yanming ; Min, Jinrong. / Structural and histone binding ability characterizations of human PWWP domains. In: PloS one. 2011 ; Vol. 6, No. 6.
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abstract = "Background: The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. Methodology/Principal Findings: The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. Conclusions: PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical β-barrel core, an insertion motif between the second and third β-strands and a C-terminal α-helix bundle. Both the canonical β-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones. Enhanced version: This article can also be viewed as an (http://www.plosone.org/enhanced/pone.0018919) in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.",
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Wu, H, Zeng, H, Lam, R, Tempel, W, Amaya, MF, Xu, C, Dombrovski, L, Qiu, W, Wang, Y & Min, J 2011, 'Structural and histone binding ability characterizations of human PWWP domains', PloS one, vol. 6, no. 6, e18919. https://doi.org/10.1371/journal.pone.0018919

Structural and histone binding ability characterizations of human PWWP domains. / Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Amaya, Maria F.; Xu, Chao; Dombrovski, Ludmila; Qiu, Wei; Wang, Yanming; Min, Jinrong.

In: PloS one, Vol. 6, No. 6, e18919, 28.06.2011.

Research output: Contribution to journalArticle

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T1 - Structural and histone binding ability characterizations of human PWWP domains

AU - Wu, Hong

AU - Zeng, Hong

AU - Lam, Robert

AU - Tempel, Wolfram

AU - Amaya, Maria F.

AU - Xu, Chao

AU - Dombrovski, Ludmila

AU - Qiu, Wei

AU - Wang, Yanming

AU - Min, Jinrong

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Y1 - 2011/6/28

N2 - Background: The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. Methodology/Principal Findings: The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. Conclusions: PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical β-barrel core, an insertion motif between the second and third β-strands and a C-terminal α-helix bundle. Both the canonical β-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones. Enhanced version: This article can also be viewed as an (http://www.plosone.org/enhanced/pone.0018919) in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

AB - Background: The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. Methodology/Principal Findings: The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. Conclusions: PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical β-barrel core, an insertion motif between the second and third β-strands and a C-terminal α-helix bundle. Both the canonical β-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones. Enhanced version: This article can also be viewed as an (http://www.plosone.org/enhanced/pone.0018919) in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1.

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