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. 2008 Jan;17(1):171-5.
doi: 10.1110/ps.073097308. Epub 2007 Nov 27.

Solution NMR studies of apo-mSin3A and -mSin3B reveal that the PAH1 and PAH2 domains are structurally independent

Yuan He  1 , Ishwar Radhakrishnan
Affiliations

Solution NMR studies of apo-mSin3A and -mSin3B reveal that the PAH1 and PAH2 domains are structurally independent

Yuan He et al. Protein Sci. 2008 Jan.

Abstract

The evolutionarily conserved mammalian Sin3 (mSin3) transcriptional corepressor interacts with a diverse array of transcription factors mainly through two PAH (paired amphipathic helix) domains located near the N terminus. Previous studies suggested the possibility of interdomain interactions involving the PAH domains. Here, we show that the domains are structurally independent and the properties of the individual domains, such as the conformational heterogeneity and the ability of mSin3A PAH2 to homodimerize, are preserved in constructs that span both PAH domains. Our results thus suggest that the N-terminal segments of the Sin3 proteins are broadly available for interactions with other proteins and that the PAH domains are organized into structurally independent modules. Our data also rule out any heterotypic association between the paralogous mSin3A and mSin3B proteins via interactions involving the mSin3A PAH2 domain.

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Figures

Figure 1.
Figure 1.
NMR spectra of the N-terminal PAH domains of mSin3A and mSin3B reveal the absence of intramolecular interactions between the domains. (A) 1H-15N correlated spectra of the mSin3A PAH2 (red), mSin3A PAH1/PAH2 (green), and an overlay of the two spectra (right) recorded at 25°C in 20 mM sodium phosphate buffer (pH 6.0). Protein concentrations were 0.35 mM, and identical NMR data acquisition, processing, display, and contouring threshold parameters were used. (B) Expanded plots corresponding to the glycine region (gray boxes) of the spectra shown in panel A. The assignments for the glycine residues in the two conformers (designated A and B) are shown (Zhang et al. 2006). (C) 1H-15N correlated spectra of mSin3B PAH2 (magenta), mSin3B PAH1/PAH2 (cyan), and an overlay of the two spectra (right) recorded at 25°C in 20 mM sodium phosphate buffer (pH 6.0). Protein concentrations were 0.24 mM, and identical NMR data acquisition, processing, display, and contouring threshold parameters were used.
See this image and copyright information in PMC

References

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