PDBsum entry 2dyf

Protein binding

PDB id: 2dyf

Contents

Protein chain

30 a.a. *

Ligands

GLY-SER-THR-ALA-PRO-PRO-LEU-PRO-ARG

* Residue conservation analysis

PDB id:

2dyf

Name:

Protein binding

Title:

Solution structure of the first ww domain of fbp11 / hypa (fbp11 ww1) complexed with a pl (pplp) motif peptide ligand

Structure:

Huntingtin-interacting protein hypa/fbp11. Chain: a. Fragment: the first ww domain. Synonym: pre-mRNA-processing factor 40 homolog a, formin-binding protein 3, huntingtin yeast partner a, fas ligand-associated factor 1, ny-ren-6 antigen. Engineered: yes. Pl (pplp) motif peptide from myosin tail region-interacting protein mti1.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932.

NMR struc:

20 models

Authors:

Y.Kato,T.Miyakawa,J.Kurita,M.Tanokura

Key ref:

Y.Kato et al. (2006). Structure of FBP11 WW1-PL ligand complex reveals the mechanism of proline-rich ligand recognition by group II/III WW domains. J Biol Chem, 281, 40321-40329. PubMed id: 17065151 DOI: 10.1074/jbc.M609321200

Date:

11-Sep-06 Release date: 24-Oct-06

Protein chain

O75400  (PR40A_HUMAN) -  Pre-mRNA-processing factor 40 homolog A from Homo sapiens

Seq: 957 a.a.

Struc: 30 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1074/jbc.M609321200

J Biol Chem 281:40321-40329 (2006)

PubMed id: 17065151

Structure of FBP11 WW1-PL ligand complex reveals the mechanism of proline-rich ligand recognition by group II/III WW domains.

Y.Kato, T.Miyakawa, J.Kurita, M.Tanokura.

ABSTRACT

FBP11/HYPA is a mammalian homologue of yeast splicing factor Prp40. The first WW domain of FBP11/HYPA (FBP11 WW1) is essential for preventing severe neurological diseases such as Huntington disease and Rett syndrome and strongly resembles the WW domain of FCA, the essential regulator for flowering time control. We have solved the structure of FBP11 WW1 and a Pro-Pro-Leu-Pro ligand complex, and demonstrated the binding mechanism with mutational analysis using surface plasmon resonance. The overall structure of FBP11 WW1 in the complex form is quite similar to the structures of WW domains from Group I and IV in complexes. In addition, conformation of FBP11 WW1 does not change much upon ligand binding. The binding orientation of the ligand against FBP11 WW1 is the same as that of the Group IV WW domain-ligand complex, but opposite to that of the Group I complex. The ligand interacts with two grooves formed by surface aromatic residues. The Pro and Leu residues in the ligand interact with the grooves and the Loop I region of FBP11 WW1, respectively, which are necessary interactions for binding the ligand. Interestingly, the two aromatic grooves recognize the Pro residues in entirely different manners, which allows FBP11 WW1 to recognize shorter sequences than the SH3 domain. Combined with homology models of other WW domains, the present report shows the detailed mechanism of ligand binding by Group II/III WW domains, and provides information useful in designing drugs to treat neurodegenerative diseases.

Selected figure(s)

Figure 1.
FIGURE 1. Superimposition of 20 output structures from CYANA-2.0. Backbones of FBP11 WW1 and the PL ligand are represented in navy and salmon pink, respectively. Side chains of the ligand are colored in red. Pink side chains of FBP11 WW1 are in contact with the ligand, whereas purple ones form a small hydrophobic core. Thr-13 is shown in orange, although it is not in contact with the ligand in our structure.

Figure 2.
FIGURE 2. Configuration and model of the complex of FBP11 WW1 and the PL motif. A, the backbone of FBP11 WW1 is represented by a ribbon with some important side chains, and the PL ligand is depicted as wires. Side chains in magenta are in direct contact with the ligand. Wire in pale blue is the backbone of the ligand flanked with its side chains in yellow-green. The side chain of Thr-13 is again shown in orange. B, the surface of FBP11 WW1 is represented with the PL ligand depicted as a yellow wire. The XP groove, XP2 groove, and Ali-patch are circled with blue, navy, and green-yellow ovals, respectively. Surface representation and calculation of electrostatic potential is carried out using MOLMOL (36). The kT/e range of electrostatic surface shading is from -1.0 (red) to +1.0 (blue). C, schematic model of the ligand-binding mechanism of FBP11 WW1 to a Pro-rich ligand that forms the PPII helix. The numbering of residues corresponds to the PL motif ligand of our structure. The crosshatched surface on the XP groove is a part of the Ali-patch. Pro-5' is recognized in a perpendicular manner by the XP2 groove, whereas the XP groove grasps the Leu-7' to Pro-8' sequence in parallel with the Trp-34 plane. The side chain of Pro-6' comes in contact with an edge of the XP2 groove. The two grooves of FBP11 WW1 primarily recognize four successive residues. D, the binding mechanism of SH3 domains to a Pro-rich ligand forming the PPII helix (37). In contrast to FBP11 WW1, both XP grooves align in parallel and recognize the respective Xaa-Pro sequences in a parallel manner. In addition, the SH3 domains do not recognize a residue (indicated by green asterisk) lying between two Xaa-Pro sequences in the ligand.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 40321-40329) copyright 2006.

Figures were selected by an automated process.