PDBsum entry 2ka9

Cell adhesion

PDB id: 2ka9

Contents

Protein chain

189 a.a. *

Ligands

GLN-VAL-VAL-PRO-PHE-SER-SER-SER-VAL ×2

* Residue conservation analysis

PDB id:

2ka9

Name:

Cell adhesion

Title:

Solution structure of psd-95 pdz12 complexed with cypin peptide

Structure:

Disks large homolog 4. Chain: a. Fragment: n-terminal pdz12 domain. Synonym: postsynaptic density protein 95, psd-95, synapse-associated protein 90, sap90. Engineered: yes. Cypin peptide. Chain: b, c. Engineered: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: dlg4, dlgh4, psd95. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: synthetic peptide

NMR struc:

20 models

Authors:

W.N.Wang,J.W.Weng,X.Zhang,M.L.Liu,M.J.Zhang

Key ref:

W.Wang et al. (2009). Creating conformational entropy by increasing interdomain mobility in ligand binding regulation: a revisit to N-terminal tandem PDZ domains of PSD-95. J Am Chem Soc, 131, 787-796. PubMed id: 19072119

Date:

03-Nov-08 Release date: 23-Jun-09

Protein chain

P31016  (DLG4_RAT) -  Disks large homolog 4 from Rattus norvegicus

Seq: 724 a.a.

Struc: 189 a.a.

Enzyme reactions

• Enzyme class: E.C.?

J Am Chem Soc 131:787-796 (2009)

PubMed id: 19072119

Creating conformational entropy by increasing interdomain mobility in ligand binding regulation: a revisit to N-terminal tandem PDZ domains of PSD-95.

W.Wang, J.Weng, X.Zhang, M.Liu, M.Zhang.

ABSTRACT

The two N-terminal PDZ domains of postsynaptic density protein-95 (PDS-95 PDZ1 and PDZ2) are closely connected in tandem by a conserved peptide linker of five amino acids. The interdomain orientation between PDZ1 and PDZ2 of the ligand-free PDZ12 tandem is restrained, and this conformational arrangement facilitates the synergistic binding of PDZ12 to multimeric targets. (1) The interdomain orientation of the target-bound state of PDZ12 is not known. Here, we have solved the structure of PDZ12 in complex with its binding domain from cypin. Both chemical shift data and residual dipolar coupling measurements showed that the restrained interdomain orientation disappeared upon cypin peptide binding. NMR-based relaxation experiments revealed slow interdomain motions in the PDZ12/cypin peptide complex. Molecular dynamics simulations also showed that the PDZ12/cypin complex has larger conformational flexibility than the ligand-free PDZ12. This dramatic change of protein dynamics provides extra conformational entropy upon ligand binding, thus enhancing the ligand binding affinity of the PDZ12 tandem. Modulation of ligand binding affinity through concerted interdomain structural and dynamic rearrangements may represent a general property of multidomain scaffold proteins.