Structure and dynamics of KH domains from FBP bound to single-stranded DNA
Open Access
- 28 February 2002
- journal article
- research article
- Published by Springer Nature in Nature
- Vol. 415 (6875) , 1051-1056
- https://doi.org/10.1038/4151051a
Abstract
Gene regulation can be tightly controlled by recognition of DNA deformations that are induced by stress generated during transcription1,2,3. The KH domains of the FUSE-binding protein (FBP), a regulator of c-myc expression1,4, bind in vivo and in vitro to the single-stranded far-upstream element (FUSE), 1,500 base pairs upstream from the c-myc promoter4,5,6. FBP bound to FUSE acts through TFIIH at the promoter4. Here we report the solution structure of a complex between the KH3 and KH4 domains of FBP and a 29-base single-stranded DNA from FUSE. The KH domains recognize two sites, 9–10 bases in length, separated by 5 bases, with KH4 bound to the 5′ site and KH3 to the 3′ site. The central portion of each site comprises a tetrad of sequence 5′d-ATTC for KH4 and 5′d-TTTT for KH3. Dynamics measurements show that the two KH domains bind as articulated modules to single-stranded DNA, providing a flexible framework with which to recognize transient, moving targets.Keywords
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