2KA9

Solution structure of PSD-95 PDZ12 complexed with cypin peptide

Summary for 2KA9

• Entry DOI: 10.2210/pdb2ka9/pdb
• Descriptor: Disks large homolog 4, cypin peptide (2 entities in total)
• Functional Keywords: pdz-cypin peptide complex, tandem pdz domain, alternative splicing, cell junction, cell membrane, lipoprotein, membrane, palmitate, phosphoprotein, postsynaptic cell membrane, sh3 domain, synapse, cell adhesion
• Biological source: Rattus norvegicus (rat); More
• Cellular location: Cell membrane; Peripheral membrane protein: P31016
• Total number of polymer chains: 3
• Total formula weight: 22025.07

Authors

Wang, W.N.,Weng, J.W.,Zhang, X.,Liu, M.L.,Zhang, M.J. (deposition date: 2008-11-03, release date: 2009-06-23, Last modification date: 2024-05-29)

Primary citation

Wang, W.N.,Weng, J.W.,Zhang, X.,Liu, M.L.,Zhang, M.J.
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, 2009

PubMed 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.

PubMed: 19072119
DOI: 10.1021/ja8076022

Experimental method

SOLUTION NMR