title: Structural insights into the mechanism of negative regulation of single-box high mobility group proteins by the acidic tail domain.
abstract: 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.
authors.affiliation: From the Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom and.
authors.forename: Katherine
authors.initials: K
authors.lastname: Stott
authors.affiliation: From the Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom and.
authors.forename: Matthew
authors.initials: M
authors.lastname: Watson
authors.affiliation: From the Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom and.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bostock
authors.affiliation: the Department of Cell Biology and Plant Biochemistry, Biochemie-Zentrum Regensburg, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Mortensen
authors.affiliation: From the Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom and.
authors.forename: Andrew
authors.initials: A
authors.lastname: Travers
authors.affiliation: the Department of Cell Biology and Plant Biochemistry, Biochemie-Zentrum Regensburg, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany.
authors.forename: Klaus D
authors.initials: KD
authors.lastname: Grasser
authors.affiliation: From the Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom and jot1@cam.ac.uk.
authors.forename: Jean O
authors.initials: JO
authors.lastname: Thomas
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D004331:Drosophila melanogaster; D006609:High Mobility Group Proteins / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D010940:Plant Proteins / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D003313:Zea mays
chemical_list: D029721:Drosophila Proteins; D006609:High Mobility Group Proteins; C106685:HmgD protein, Drosophila; D050505:Mutant Proteins; D010940:Plant Proteins
keywords: Acidic Regulatory Domain; Casein Kinase 2 (CK2); Chromatin; HMGB Protein; Intrinsically Disordered Protein; Nuclear Magnetic Resonance (NMR); Paramagnetic Relaxation Enhancement; Phosphorylation; Protein Kinase C; Protein Kinase C (PKC)