Structural Insights into the Mechanism of Negative Regulation of Single-box High Mobility Group Proteins by the Acidic Tail Domain
Mortensen, Simon A
Grasser, Klaus D
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology
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Stott, K., Watson, M., Bostock, M., Mortensen, S. A., Travers, A., Grasser, K. D., & Thomas, J. (2014). Structural Insights into the Mechanism of Negative Regulation of Single-box High Mobility Group Proteins by the Acidic Tail Domain. Journal of Biological Chemistry, 289 29817-29826. https://doi.org/10.1074/jbc.M114.591115
The Drosophila and plant (maize) functional counterparts of the abundant vertebrate chromosomal protein HMGB1 (HMG-D and ZmHMGB1, respectively) differ from HMGB1 in having a single HMG box, as well as basic and acidic flanking regions that vary greatly in length and charge. We show that despite these variations, HMG-D and ZmHMGB1 exist in dynamic assemblies in which the basic HMG boxes and linkers associate with their intrinsically disordered, predominantly acidic, tails in a manner analogous to that observed previously for HMGB1. The DNA-binding surfaces of the boxes and linkers are occluded in “auto-inhibited” forms of the protein, which are in equilibrium with transient, more open structures that are “binding-competent.” This strongly suggests that the mechanism of auto-inhibition may be a general one. HMG-D and ZmHMGB1 differ from HMGB1 in having phosphorylation sites in their tail and linker regions. In both cases, in vitro phosphorylation of serine residues within the acidic tail stabilizes the assembled form, suggesting another level of regulation for interaction with DNA, chromatin, and other proteins that is not possible for the uniformly acidic (hence unphosphorylatable) tail of HMGB1.
This work was supported by the Biotechnology and Biological Sciences Research Council through the award of Grant BB/D002257/1 (to J. O. T.) and a grant from the Deutsche Forschungsgemeinschaft (DFG) (to K. D. G.).
External DOI: https://doi.org/10.1074/jbc.M114.591115
This record's URL: https://www.repository.cam.ac.uk/handle/1810/247304
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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