PDBsum entry 5izu

Protein binding

PDB id: 5izu

Contents

Protein chains

124 a.a.

15 a.a.

Waters ×95

PDB id:

5izu

Name:

Protein binding

Title:

A new binding site outside the canonical pdz domain determines the specific interaction between shank and sapap and their function

Structure:

Sh3 and multiple ankyrin repeat domains protein 3. Chain: a, c. Fragment: unp residues 533-665. Synonym: shank. Engineered: yes. Peptide from disks large-associated protein 3. Chain: b, d. Fragment: unp residues 963-977. Synonym: sapap3.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: shank3. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: c-terminal extended pbm of sapap

Resolution:

2.49Å R-factor: 0.186 R-free: 0.251

Authors:

Y.Shang,M.Zeng,M.Zhang

Key ref:

M.Zeng et al. (2016). A binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function. Proc Natl Acad Sci U S A, 113, E3081. PubMed id: 27185935 DOI: 10.1073/pnas.1523265113

Date:

26-Mar-16 Release date: 18-May-16

Protein chains

Q4ACU6  (SHAN3_MOUSE) -  SH3 and multiple ankyrin repeat domains protein 3 from Mus musculus

Seq: 1730 a.a.

Struc: 124 a.a.

Protein chains

Q6PFD5  (DLGP3_MOUSE) -  Disks large-associated protein 3 from Mus musculus

Seq: 977 a.a.

Struc: 15 a.a.

DOI no: 10.1073/pnas.1523265113

Proc Natl Acad Sci U S A 113:E3081 (2016)

PubMed id: 27185935

A binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function.

M.Zeng, Y.Shang, T.Guo, Q.He, W.H.Yung, K.Liu, M.Zhang.

ABSTRACT

Shank and SAPAP (synapse-associated protein 90/postsynaptic density-95-associated protein) are two highly abundant scaffold proteins that directly interact with each other to regulate excitatory synapse development and plasticity. Mutations of SAPAP, but not other reported Shank PDZ domain binders, share a significant overlap on behavioral abnormalities with the mutations of Shank both in patients and in animal models. The molecular mechanism governing the exquisite specificity of the Shank/SAPAP interaction is not clear, however. Here we report that a sequence preceding the canonical PDZ domain of Shank, together with the elongated PDZ BC loop, form another binding site for a sequence upstream of the SAPAP PDZ-binding motif, leading to a several hundred-fold increase in the affinity of the Shank/SAPAP interaction. We provide evidence that the specific interaction afforded by this newly identified site is required for Shank synaptic targeting and the Shank-induced synaptic activity increase. Our study provides a molecular explanation of how Shank and SAPAP dosage changes due to their gene copy number variations can contribute to different psychiatric disorders.