2JXW

Solution Structure of the Tandem WW Domains of FBP21

Summary for 2JXW

• Entry DOI: 10.2210/pdb2jxw/pdb
• NMR Information: BMRB: 15575
• Descriptor: WW domain-binding protein 4 (1 entity in total)
• Functional Keywords: ww domain containing protein, ww domain, fbp21, wbp4, metal-binding, mrna processing, mrna splicing, nucleus, polymorphism, spliceosome, zinc, zinc-finger, formin binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 8688.31

Authors

Huang, X.,Zhang, J.,Wu, J.,Shi, Y. (deposition date: 2007-11-30, release date: 2008-12-02, Last modification date: 2024-05-15)

Primary citation

Huang, X.,Beullens, M.,Zhang, J.,Zhou, Y.,Nicolaescu, E.,Lesage, B.,Hu, Q.,Wu, J.,Bollen, M.,Shi, Y.
Structure and function of the two tandem WW domains of the pre-mRNA splicing factor FBP21 (formin-binding protein 21)
J.Biol.Chem., 284:25375-25387, 2009

PubMed Abstract: Human FBP21 (formin-binding protein 21) contains a matrin-type zinc finger and two tandem WW domains. It is a component of the spliceosomes and interacts with several established splicing factors. Here we demonstrate for the first time that FBP21 is an activator of pre-mRNA splicing in vivo and that its splicing activation function and interaction with the splicing factor SIPP1 (splicing factor that interacts with PQBP1 and PP1) are both mediated by the two tandem WW domains of group III. We determined the solution structure of the tandem WW domains of FBP21 and found that the WW domains recognize peptide ligands containing either group II (PPLP) or group III (PPR) motifs. The binding interfaces involve both the XP and XP2 grooves of the two WW domains. Significantly, the tandem WW domains of FBP21 are connected by a highly flexible region, enabling their simultaneous interaction with two proline-rich motifs of SIPP1. The strong interaction between SIPP1 and FBP21 can be explained by the conjugation of two low affinity interactions with the tandem WW domains. Our study provides a structural basis for understanding the molecular mechanism underlying the functional implication of FBP21 and the biological specificity of tandem WW domains.

PubMed: 19592703
DOI: 10.1074/jbc.M109.024828

Experimental method

SOLUTION NMR