Structure of a novel winged-helix like domain from human NFRKB protein

• Published in: PloS one 2012-09, Vol.7 (9), p.e43761-e43761
• Main Authors: Kumar, Abhinav, Möcklinghoff, Sabine, Yumoto, Fumiaki, Jaroszewski, Lukasz, Farr, Carol L, Grzechnik, Anna, Nguyen, Phuong, Weichenberger, Christian X, Chiu, Hsiu-Ju, Klock, Heath E, Elsliger, Marc-André, Deacon, Ashley M, Godzik, Adam, Lesley, Scott A, Conklin, Bruce R, Fletterick, Robert J, Wilson, Ian A
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analysis; Automation; Bacterial Proteins - chemistry; BASIC BIOLOGICAL SCIENCES; Biochemistry; Bioinformatics; Biology; Biophysics; Cardiovascular disease; Chromatin; Chromatin remodeling; Crystal structure; Crystallography; Crystallography, X-Ray; Cullin Proteins - chemistry; Deoxyribonucleic acid; Distributed control systems; DNA; DNA - metabolism; DNA biosynthesis; DNA methylation; DNA repair; DNA replication; DNA structure; DNA-binding proteins; DNA-Binding Proteins - chemistry; Gene regulation; Genomics; Humans; Laboratories; Medical research; Molecular biology; Molecular Sequence Data; Protein Binding; Protein Denaturation; Protein domains; Protein interaction; Protein Interaction Maps; Protein structure; Protein structure databases; Protein structure determination; Protein structure prediction; Protein Structure, Secondary; Protein Structure, Tertiary; Protein-protein interactions; Proteins; Repressor Proteins - chemistry; Saccharomyces cerevisiae - chemistry; Sequence Alignment; Structural Homology, Protein; Temperature; Transcription; Transcription (Genetics); Winged-Helix Transcription Factors - chemistry
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0043761

The human nuclear factor related to kappa-B-binding protein (NFRKB) is a 1299-residue protein that is a component of the metazoan INO80 complex involved in chromatin remodeling, transcription regulation, DNA replication and DNA repair. Although full length NFRKB is predicted to be around 65% disordered, comparative sequence analysis identified several potentially structured sections in the N-terminal region of the protein. These regions were targeted for crystallographic studies, and the structure of one of these regions spanning residues 370-495 was determined using the JCSG high-throughput structure determination pipeline. The structure reveals a novel, mostly helical domain reminiscent of the winged-helix fold typically involved in DNA binding. However, further analysis shows that this domain does not bind DNA, suggesting it may belong to a small group of winged-helix domains involved in protein-protein interactions.