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Title: Two high-mobility group box domains act together to underwind and kink DNA

The crystal structure of HMGB1 box A bound to an unmodified AT-rich DNA fragment is reported at a resolution of 2 Å. A new mode of DNA recognition for HMG box proteins is found in which two box A domains bind in an unusual configuration generating a highly kinked DNA structure. 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 linearmore » DNA.« less
Authors:
;  [1] ;  [2] ;  [1] ;  [2] ;  [1]
  1. Universitat Politecnica de Catalunya, 08028 Barcelona (Spain)
  2. University of Colorado School of Medicine, Aurora, CO 80045 (United States)
Publication Date:
OSTI Identifier:
22389070
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section D: Biological Crystallography; Journal Volume: 71; Journal Issue: Pt 7; Other Information: PMCID: PMC4498601; PMID: 26143914; PUBLISHER-ID: mh5175; OAI: oai:pubmedcentral.nih.gov:4498601; Copyright (c) Sánchez-Giraldo et al. 2015; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; CLATHRATES; CONFIGURATION; CRYSTAL STRUCTURE; CRYSTALS; DNA; INTERACTIONS; MOBILITY; PROTEINS; RESOLUTION; SPECIFICITY