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The structural basis for the oligomerization of the N-terminal domain of SATB1.

Wang Z, Yang X, Chu X, Zhang J, Zhou H, Shen Y, Long J - Nucleic Acids Res. (2012)

Bottom Line: Our results also reveal that SATB1 can form a tetramer through its N-terminal domain.Furthermore, isothermal titration calorimetry results indicate that the SATB1 tetramer can bind simultaneously to two DNA targets.Based on these results, we propose a molecular model whereby SATB1 regulates the expression of multiple genes both locally and at a distance.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.

ABSTRACT
Special AT-rich sequence-binding protein 1 (SATB1) is a global chromatin organizer and gene expression regulator essential for T-cell development and breast cancer tumor growth and metastasis. The oligomerization of the N-terminal domain of SATB1 is critical for its biological function. We determined the crystal structure of the N-terminal domain of SATB1. Surprisingly, this domain resembles a ubiquitin domain instead of the previously proposed PDZ domain. Our results also reveal that SATB1 can form a tetramer through its N-terminal domain. The tetramerization of SATB1 plays an essential role in its binding to highly specialized DNA sequences. Furthermore, isothermal titration calorimetry results indicate that the SATB1 tetramer can bind simultaneously to two DNA targets. Based on these results, we propose a molecular model whereby SATB1 regulates the expression of multiple genes both locally and at a distance.

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Interface of the SATB1 ULD homotetramer. (A) Ribbon diagram of a representative SATB1 ULD homotetramer. The four individual ULDs are colored red, cyan, green and yellow. Schematic diagrams showing the detailed interactions within the cyan–yellow dimer (B) and the green–yellow dimer (C). The color of the residues within each dimer interface is same as that of the individual ULDs in (A). Hydrogen bonds and hydrophobic interactions are shown as red and gray dotted lines, respectively.
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gkr1284-F2: Interface of the SATB1 ULD homotetramer. (A) Ribbon diagram of a representative SATB1 ULD homotetramer. The four individual ULDs are colored red, cyan, green and yellow. Schematic diagrams showing the detailed interactions within the cyan–yellow dimer (B) and the green–yellow dimer (C). The color of the residues within each dimer interface is same as that of the individual ULDs in (A). Hydrogen bonds and hydrophobic interactions are shown as red and gray dotted lines, respectively.

Mentions: Our crystal structure contains four ULD molecules, which seem to form a tightly packed tetramer, in one asymmetric unit (Figure 2A). Consistent with this observation, ULD was eluted as a single peak from a size exclusion column with a molecular mass corresponding to a tetramer (Supplementary Figure S4A). Analytical ultracentrifugation further confirmed that ULD assembles into a tetramer with a molecular mass of ∼43.5 kDa (Supplementary Figure S4B). These results demonstrate that ULD forms a homotetramer in solution.Figure 2.


The structural basis for the oligomerization of the N-terminal domain of SATB1.

Wang Z, Yang X, Chu X, Zhang J, Zhou H, Shen Y, Long J - Nucleic Acids Res. (2012)

Interface of the SATB1 ULD homotetramer. (A) Ribbon diagram of a representative SATB1 ULD homotetramer. The four individual ULDs are colored red, cyan, green and yellow. Schematic diagrams showing the detailed interactions within the cyan–yellow dimer (B) and the green–yellow dimer (C). The color of the residues within each dimer interface is same as that of the individual ULDs in (A). Hydrogen bonds and hydrophobic interactions are shown as red and gray dotted lines, respectively.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351170&req=5

gkr1284-F2: Interface of the SATB1 ULD homotetramer. (A) Ribbon diagram of a representative SATB1 ULD homotetramer. The four individual ULDs are colored red, cyan, green and yellow. Schematic diagrams showing the detailed interactions within the cyan–yellow dimer (B) and the green–yellow dimer (C). The color of the residues within each dimer interface is same as that of the individual ULDs in (A). Hydrogen bonds and hydrophobic interactions are shown as red and gray dotted lines, respectively.
Mentions: Our crystal structure contains four ULD molecules, which seem to form a tightly packed tetramer, in one asymmetric unit (Figure 2A). Consistent with this observation, ULD was eluted as a single peak from a size exclusion column with a molecular mass corresponding to a tetramer (Supplementary Figure S4A). Analytical ultracentrifugation further confirmed that ULD assembles into a tetramer with a molecular mass of ∼43.5 kDa (Supplementary Figure S4B). These results demonstrate that ULD forms a homotetramer in solution.Figure 2.

Bottom Line: Our results also reveal that SATB1 can form a tetramer through its N-terminal domain.Furthermore, isothermal titration calorimetry results indicate that the SATB1 tetramer can bind simultaneously to two DNA targets.Based on these results, we propose a molecular model whereby SATB1 regulates the expression of multiple genes both locally and at a distance.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin 300071, China.

ABSTRACT
Special AT-rich sequence-binding protein 1 (SATB1) is a global chromatin organizer and gene expression regulator essential for T-cell development and breast cancer tumor growth and metastasis. The oligomerization of the N-terminal domain of SATB1 is critical for its biological function. We determined the crystal structure of the N-terminal domain of SATB1. Surprisingly, this domain resembles a ubiquitin domain instead of the previously proposed PDZ domain. Our results also reveal that SATB1 can form a tetramer through its N-terminal domain. The tetramerization of SATB1 plays an essential role in its binding to highly specialized DNA sequences. Furthermore, isothermal titration calorimetry results indicate that the SATB1 tetramer can bind simultaneously to two DNA targets. Based on these results, we propose a molecular model whereby SATB1 regulates the expression of multiple genes both locally and at a distance.

Show MeSH
Related in: MedlinePlus