title: Two high-mobility group box domains act together to underwind and kink DNA.
abstract: High-mobility group protein 1 (HMGB1) is an essential and ubiquitous DNA architectural factor that influences a myriad of cellular processes. HMGB1 contains two DNA-binding domains, box A and box B, which have little sequence specificity but have remarkable abilities to underwind and bend DNA. Although HMGB1 box A is thought to be responsible for the majority of HMGB1-DNA interactions with pre-bent or kinked DNA, little is known about how it recognizes unmodified DNA. Here, the crystal structure of HMGB1 box A bound to an AT-rich DNA fragment is reported at a resolution of 2 Å. Two box A domains of HMGB1 collaborate in an unusual configuration in which the Phe37 residues of both domains stack together and intercalate the same CG base pair, generating highly kinked DNA. This represents a novel mode of DNA recognition for HMGB proteins and reveals a mechanism by which structure-specific HMG boxes kink linear DNA.
authors.affiliation: Departament d'Enginyeria Quimica, Universitat Politecnica de Catalunya, 08028 Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Sánchez-Giraldo
authors.affiliation: Departament d'Enginyeria Quimica, Universitat Politecnica de Catalunya, 08028 Barcelona, Spain.
authors.forename: F J
authors.initials: FJ
authors.lastname: Acosta-Reyes
authors.affiliation: Department of Pharmacology and the Program in Structural Biology and Biochemistry, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: C S
authors.initials: CS
authors.lastname: Malarkey
authors.affiliation: Departament d'Enginyeria Quimica, Universitat Politecnica de Catalunya, 08028 Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Saperas
authors.affiliation: Department of Pharmacology and the Program in Structural Biology and Biochemistry, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: M E A
authors.initials: ME
authors.lastname: Churchill
authors.affiliation: Departament d'Enginyeria Quimica, Universitat Politecnica de Catalunya, 08028 Barcelona, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Campos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D024742:HMG-Box Domains; D024243:HMGB1 Protein / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D051381:Rats; D016415:Sequence Alignment
chemical_list: D024243:HMGB1 Protein; C015314:kinked DNA; D004247:DNA
keywords: DNA binding; HMGB1; X-ray crystallography; high-mobility group protein