PDBsum entry 2jxw

Formin binding protein

PDB id: 2jxw

Contents

Protein chain

75 a.a. *

* Residue conservation analysis

PDB id:

2jxw

Name:

Formin binding protein

Title:

Solution structure of the tandem ww domains of fbp21

Structure:

Ww domain-binding protein 4. Chain: a. Fragment: ww domian. Synonym: wbp-4, ww domain-containing-binding protein 4, formin- binding protein 21, fbp21. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: wbp4, fbp21, fnbp21. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

X.Huang,J.Zhang,J.Wu,Y.Shi

Key ref:

X.Huang et al. (2009). 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. PubMed id: 19592703 DOI: 10.1074/jbc.M109.024828

Date:

30-Nov-07 Release date: 02-Dec-08

Protein chain

O75554  (WBP4_HUMAN) -  WW domain-binding protein 4 from Homo sapiens

Seq: 376 a.a.

Struc: 75 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M109.024828

J Biol Chem 284:25375-25387 (2009)

PubMed id: 19592703

Structure and function of the two tandem WW domains of the pre-mRNA splicing factor FBP21 (formin-binding protein 21).

X.Huang, M.Beullens, J.Zhang, Y.Zhou, E.Nicolaescu, B.Lesage, Q.Hu, J.Wu, M.Bollen, Y.Shi.

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.

Selected figure(s)

Figure 1.
Domain structure of human FBP21 and SIPP1, as predicted by PROSITE.

Figure 5.
Solution structure of the tandem WW domains of FBP21.A, sequence alignment of FBP21 tandem WW domains with its orthologues as follows: Hs.FBP21 and Hs.FBP11 from Homo sapiens; Mm.FBP21 and Mm.HYPC from Mus musculus; and Sc.PRP40 from Saccharomyces cerevisiae. The WW domain boundaries are indicated by boxes at the top, and the secondary structure elements are boxed and indicated above the alignment. Residues identical in all five sequences are shown in red columns, and conserved residues are shown in red letters. Stars indicate residues forming binding interface. The sequence alignment was made using ClustalW, and the panel was generated by ESPript 2.2. B, ribbon representation of two structures in different interdomain orientations with secondary elements of WW domains shown as turquoise arrows. C, stereoview of the 20 lowest energy NMR structures of FBP21 tandem WW domains, superimposed on backbone atoms of WW1 (blue) and WW2 (green), respectively, and the flexible linker is shown in magenta. The structures cannot be superimposed over the entire molecule due to the flexible interdomain motion. D, view of the binding surface on the tandem WW domains of FBP21. Residues that form the XP and XP2 grooves are shown as green and purple sticks, respectively. The side chains of residues forming a hydrophobic core that stabilizes the fold are shown in yellow. The figures were made using MOLMOL and PyMol. E, space-filling structure of the WW domains of FBP21. The molecular surface is colored according to electric and hydrophobic potential. Blue colors represent positive charges; red colors are negative charges; neutral areas are gray, and yellow represents hydrophobic residues. The green and purple circles represent the XP and XP2 grooves, respectively.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2009, 284, 25375-25387) copyright 2009.

Figures were selected by an automated process.