The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation

Citation
Mj. Bottomley et al., The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation, NAT ST BIOL, 8(7), 2001, pp. 626-633
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NATURE STRUCTURAL BIOLOGY
ISSN journal
1072-8368 → ACNP
Volume
8
Issue
7
Year of publication
2001
Pages
626 - 633
Database
ISI
SICI code
1072-8368(200107)8:7<626:TSDSDA>2.0.ZU;2-R
Abstract
The SAND domain is a conserved sequence motif found in a number of nuclear proteins, including the Sp100 family and NUDR. These are thought to play im portant roles in chromatin-dependent transcriptional regulation and are lin ked to many diseases. We have determined the three-dimensional (3D) structu re of the SAND domain from Sp100b. The structure represents a novel alpha/b eta fold, in which a conserved KDWK sequence motif is found within an a-hel ical, positively charged surface patch. For NUDR, the SAND domain is shown to be sufficient to mediate DNA binding. Using mutational analyses and chem ical shift perturbation experiments, the DNA binding surface is mapped to t he a-helical region encompassing the KDWK motif. The DNA binding activity o f wild type and mutant proteins in vitro correlates with transcriptional re gulation activity of full length NUDR in vivo. The evolutionarily conserved SAND domain defines a new DNA binding fold that is involved in chromatin-a ssociated transcriptional regulation.