RESUMO
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 2â 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.
Assuntos
DNA/metabolismo , Domínios HMG-Box , Proteína HMGB1/química , Proteína HMGB1/metabolismo , Sequência de Aminoácidos , Animais , Cristalografia por Raios X , DNA/química , Modelos Moleculares , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Conformação Proteica , Ratos , Alinhamento de SequênciaRESUMO
Poor oral health is an extremely common problem in patients with advanced cancer and, because of its impact on quality of life, promoting oral care should be regarded as a priority by every hospice and palliative care team. At Accord Hospice, Paisley, UK, a protocol for oral care has been developed which is simple, inexpensive and evidence-based. Evaluation of the protocol has shown that it can lead to significant and consistent improvements in oral health and comfort. A survey of mouth-care practices in other Scottish hospice units reveals that although much agreement exists, certain practices that are unsupported by research evidence are still undertaken.
