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Recognition of asymmetrically dimethylated arginine by TDRD3.

Sikorsky T, Hobor F, Krizanova E, Pasulka J, Kubicek K, Stefl R - Nucleic Acids Res. (2012)

Bottom Line: The structure and mutational analysis provide a molecular basis for how TDRD3 recognizes the aDMA mark.The unique aromatic cavity of the TDRD3 Tudor domain with a tyrosine in position 566 creates a selectivity filter for the aDMA residue.Our work contributes to the understanding of substrate selectivity rules of the Tudor aromatic cavity, which is an important structural motif for reading of methylation marks.

View Article: PubMed Central - PubMed

Affiliation: CEITEC-Central European Institute of Technology, Masaryk University, CZ-62500 Brno, Czech Republic.

ABSTRACT
Asymmetric dimethylarginine (aDMA) marks are placed on histones and the C-terminal domain (CTD) of RNA Polymerase II (RNAP II) and serve as a signal for recruitment of appropriate transcription and processing factors in coordination with transcription cycle. In contrast to other Tudor domain-containing proteins, Tudor domain-containing protein 3 (TDRD3) associates selectively with the aDMA marks but not with other methylarginine motifs. Here, we report the solution structure of the Tudor domain of TDRD3 bound to the asymmetrically dimethylated CTD. The structure and mutational analysis provide a molecular basis for how TDRD3 recognizes the aDMA mark. The unique aromatic cavity of the TDRD3 Tudor domain with a tyrosine in position 566 creates a selectivity filter for the aDMA residue. Our work contributes to the understanding of substrate selectivity rules of the Tudor aromatic cavity, which is an important structural motif for reading of methylation marks.

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NMR structure of the TDRD3 Tudor–aDMA-CTD complex. (A) Overlay of the 20 lowest energy structures of the TDRD3 Tudor–aDMA-CTD complex shown in stereo view. Backbone and side-chains of the aromatic cavity (Y566, Y573, F591 and Y594) are shown in wire representation. For clarity, only aDMA residue of the bound peptide is shown in wire representation. The TDRD3 Tudor domain and aDMA are shown in black and red, respectively. (B) Structure of the human TDRD3 Tudor domain bound to the aDMA-CTD peptide. The aDMA-CTD peptide is represented as a magenta ribbon with the aDMA residue in sticks (only methyl protons are shown) and the protein is shown as a blue ribbon model. Residues forming the aromatic cavity (Y566, Y573, F591 and Y594) are shown in green sticks and the cube-shaped cavity is highlighted by a square. (C) aDMA recognition by the TDRD3 Tudor domains. The hydrogen bond and aDMA interactions with the aromatic cavity are shown with yellow dotted lines. Only aDMA and the side-chain of amino acids that form, or interact with the aromatic cavity are shown (starting from Cα atoms).
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gks929-F2: NMR structure of the TDRD3 Tudor–aDMA-CTD complex. (A) Overlay of the 20 lowest energy structures of the TDRD3 Tudor–aDMA-CTD complex shown in stereo view. Backbone and side-chains of the aromatic cavity (Y566, Y573, F591 and Y594) are shown in wire representation. For clarity, only aDMA residue of the bound peptide is shown in wire representation. The TDRD3 Tudor domain and aDMA are shown in black and red, respectively. (B) Structure of the human TDRD3 Tudor domain bound to the aDMA-CTD peptide. The aDMA-CTD peptide is represented as a magenta ribbon with the aDMA residue in sticks (only methyl protons are shown) and the protein is shown as a blue ribbon model. Residues forming the aromatic cavity (Y566, Y573, F591 and Y594) are shown in green sticks and the cube-shaped cavity is highlighted by a square. (C) aDMA recognition by the TDRD3 Tudor domains. The hydrogen bond and aDMA interactions with the aromatic cavity are shown with yellow dotted lines. Only aDMA and the side-chain of amino acids that form, or interact with the aromatic cavity are shown (starting from Cα atoms).

Mentions: To understand the structural basis for molecular recognition of aDMA-containing CTD by TDRD3, we determined the solution structure of a reconstituted complex consisting of the Tudor domain of TDRD3 (residues 555–610) and a 13-mer peptide aDMA-CTD [YSPSSP(aDMA)YTPQSP; Figure 1A] (Figure 2A and B; Supplementary Figure S2B and C; Supplementary Table S1). The Tudor domain of TDRD3 forms a four-stranded β-barrel fold and is similar to the structure of TDRD3 in free form (Supplementary Figure S2B) (25).Figure 2.


Recognition of asymmetrically dimethylated arginine by TDRD3.

Sikorsky T, Hobor F, Krizanova E, Pasulka J, Kubicek K, Stefl R - Nucleic Acids Res. (2012)

NMR structure of the TDRD3 Tudor–aDMA-CTD complex. (A) Overlay of the 20 lowest energy structures of the TDRD3 Tudor–aDMA-CTD complex shown in stereo view. Backbone and side-chains of the aromatic cavity (Y566, Y573, F591 and Y594) are shown in wire representation. For clarity, only aDMA residue of the bound peptide is shown in wire representation. The TDRD3 Tudor domain and aDMA are shown in black and red, respectively. (B) Structure of the human TDRD3 Tudor domain bound to the aDMA-CTD peptide. The aDMA-CTD peptide is represented as a magenta ribbon with the aDMA residue in sticks (only methyl protons are shown) and the protein is shown as a blue ribbon model. Residues forming the aromatic cavity (Y566, Y573, F591 and Y594) are shown in green sticks and the cube-shaped cavity is highlighted by a square. (C) aDMA recognition by the TDRD3 Tudor domains. The hydrogen bond and aDMA interactions with the aromatic cavity are shown with yellow dotted lines. Only aDMA and the side-chain of amino acids that form, or interact with the aromatic cavity are shown (starting from Cα atoms).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3526276&req=5

gks929-F2: NMR structure of the TDRD3 Tudor–aDMA-CTD complex. (A) Overlay of the 20 lowest energy structures of the TDRD3 Tudor–aDMA-CTD complex shown in stereo view. Backbone and side-chains of the aromatic cavity (Y566, Y573, F591 and Y594) are shown in wire representation. For clarity, only aDMA residue of the bound peptide is shown in wire representation. The TDRD3 Tudor domain and aDMA are shown in black and red, respectively. (B) Structure of the human TDRD3 Tudor domain bound to the aDMA-CTD peptide. The aDMA-CTD peptide is represented as a magenta ribbon with the aDMA residue in sticks (only methyl protons are shown) and the protein is shown as a blue ribbon model. Residues forming the aromatic cavity (Y566, Y573, F591 and Y594) are shown in green sticks and the cube-shaped cavity is highlighted by a square. (C) aDMA recognition by the TDRD3 Tudor domains. The hydrogen bond and aDMA interactions with the aromatic cavity are shown with yellow dotted lines. Only aDMA and the side-chain of amino acids that form, or interact with the aromatic cavity are shown (starting from Cα atoms).
Mentions: To understand the structural basis for molecular recognition of aDMA-containing CTD by TDRD3, we determined the solution structure of a reconstituted complex consisting of the Tudor domain of TDRD3 (residues 555–610) and a 13-mer peptide aDMA-CTD [YSPSSP(aDMA)YTPQSP; Figure 1A] (Figure 2A and B; Supplementary Figure S2B and C; Supplementary Table S1). The Tudor domain of TDRD3 forms a four-stranded β-barrel fold and is similar to the structure of TDRD3 in free form (Supplementary Figure S2B) (25).Figure 2.

Bottom Line: The structure and mutational analysis provide a molecular basis for how TDRD3 recognizes the aDMA mark.The unique aromatic cavity of the TDRD3 Tudor domain with a tyrosine in position 566 creates a selectivity filter for the aDMA residue.Our work contributes to the understanding of substrate selectivity rules of the Tudor aromatic cavity, which is an important structural motif for reading of methylation marks.

View Article: PubMed Central - PubMed

Affiliation: CEITEC-Central European Institute of Technology, Masaryk University, CZ-62500 Brno, Czech Republic.

ABSTRACT
Asymmetric dimethylarginine (aDMA) marks are placed on histones and the C-terminal domain (CTD) of RNA Polymerase II (RNAP II) and serve as a signal for recruitment of appropriate transcription and processing factors in coordination with transcription cycle. In contrast to other Tudor domain-containing proteins, Tudor domain-containing protein 3 (TDRD3) associates selectively with the aDMA marks but not with other methylarginine motifs. Here, we report the solution structure of the Tudor domain of TDRD3 bound to the asymmetrically dimethylated CTD. The structure and mutational analysis provide a molecular basis for how TDRD3 recognizes the aDMA mark. The unique aromatic cavity of the TDRD3 Tudor domain with a tyrosine in position 566 creates a selectivity filter for the aDMA residue. Our work contributes to the understanding of substrate selectivity rules of the Tudor aromatic cavity, which is an important structural motif for reading of methylation marks.

Show MeSH
Related in: MedlinePlus