Crystal Structure of the Three Tandem FF Domains of the Transcription Elongation Regulator CA150

JOURNAL OF MOLECULAR BIOLOGY

卷:393

Article

Lu, Ming^1,2  Yang, Jun^1,2  Ren, Zhiyong¹  Sabui, Subir³  Espejo, Alexsandra⁴  Bedford, Mark T.^2,4  Jacobson, Raymond H.^1,2  Jeruzalmi, David⁵  McMurray, John S.^2,3  Chen, Xiaomin^1,2 

[1] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA

[2] Univ Texas Hlth Sci Ctr, Grad Sch Biomed Sci, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX 78957 USA

[5] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA

关键词: FF domain;    CA150;    X-ray crystallography;    protein-ligand interaction;    transcription;   

DOI  :  10.1016/j.jmb.2009.07.086

来源: Elsevier

【 摘 要 】

FF domains are small protein-protein interaction modules that have two flanking conserved phenylalanine residues. They are present in proteins involved in transcription, RNA splicing, and signal transduction, and often exist in tandem arrays. Although several individual FF domain structures have been determined by NMR, the tandem nature of most FF domains has not been revealed. Here we report the 2.7-angstrom-resolution crystal structure of the first three FF domains of the human transcription elongation factor CA150. Each FF domain is composed of three alpha-helices and a 3(10) helix between alpha-helix 2 and alpha-helix 3. The most striking feature of the structure is that an FF domain is connected to the next by an alpha-helix that continues from helix 3 to helix 1 of the next. The consequent elongated arrangement allows exposure of many charged residues within the region that can be engaged in interaction with other molecules. Binding studies using a peptide ligand suggest that a specific conformation of the FF domains might be required to achieve higher-affinity binding. Additionally, we explore potential DNA binding of the FF construct used in this study. Overall, we provide the first crystal structure of an FF domain and insights into the tandem nature of the FF domains and suggest that, in addition to protein binding, FF domains might be involved in DNA binding. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

Free