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Finding the function buried in SAND

Nature Structural Biology volume 8, pages 568–570 (2001)Cite this article

The SAND domain is present in many proteins that have been linked to chromatin-dependent transcriptional regulation and human disease, but their function has remained unknown. Recent studies have revealed that these modules are DNA binding domains of novel molecular structure.

Multicomponent complexes differentially control the expression of specific genes by modulating the activities of chromatin-modifying complexes and the transcription apparatus. Which genes are to be activated or repressed depends on transcription factor recognition of cis-acting nucleotide sequences, which synergistically work with other proteins to modulate transcription. Over the past 20 years structural biologists have discovered Nature's frugality; almost all transcription factors specifically bind DNA using a common set of structurally conserved motifs (helix-turn-helix, helix-loop-helix, and so forth), which are presented to the duplex in the context of an autonomously folded domain. Now, on page 626 of this issue of Nature Structural Biology, the Sattler group presents work on a new family of DNA binding proteins that defy classification, the SAND domains1. In the process they conclusively show that SAND domains are bona fide DNA binding proteins, shedding considerable light onto their functional role in transcription and in several disease related proteins of unknown function.

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Figure 1: SAND domain contexts and functions.
Figure 2: Do SAND domains recognize the major groove in a manner reminiscent of the helix-turn-helix proteins?

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Acknowledgements

J.M.W. and R.T.C. are supported by grants from the National Institutes of Health and Department of Energy.

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  1. the Department of Chemistry and Biochemistry, Molecular Biology Institute and the UCLA-DOE Laboratory of Structural Biology and Molecular Medicine, University of California, Los Angeles, 405 Hilgard Ave, Los Angeles, 90095-1570, California, USA

    Jonathan M. Wojciak & Robert T. Clubb

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Correspondence to Robert T. Clubb.

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Wojciak, J., Clubb, R. Finding the function buried in SAND. Nat Struct Mol Biol 8, 568–570 (2001). https://doi.org/10.1038/89582

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