PDBsum entry 4wsi

Peptide binding protein

PDB id: 4wsi

Contents

Protein chains

372 a.a.

18 a.a.

Waters ×20

PDB id:

4wsi

Name:

Peptide binding protein

Title:

Crystal structure of pals1/crb complex

Structure:

Maguk p55 subfamily member 5. Chain: a, b. Fragment: unp residues 236-410, 460-675. Engineered: yes. Protein crumbs. Chain: x, y. Fragment: unp residues 2111-2146. Synonym: 95f. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mpp5. Expressed in: escherichia coli. Expression_system_taxid: 562. Drosophila melanogaster. Fruit fly. Organism_taxid: 7227.

Resolution:

2.95Å R-factor: 0.208 R-free: 0.235

Authors:

Z.Wei,Y.Li,M.Zhang

Key ref:

Y.Li et al. (2014). Structure of Crumbs tail in complex with the PALS1 PDZ-SH3-GK tandem reveals a highly specific assembly mechanism for the apical Crumbs complex. Proc Natl Acad Sci U S A, 111, 17444-17449. PubMed id: 25385611 DOI: 10.1073/pnas.1416515111

Date:

28-Oct-14 Release date: 26-Nov-14

Protein chains

Q8N3R9  (MPP5_HUMAN) -  Protein PALS1 from Homo sapiens

Seq: 675 a.a.

Struc: 372 a.a.

Protein chains

P10040  (CRB_DROME) -  Protein crumbs from Drosophila melanogaster

Seq: 2146 a.a.

Struc: 18 a.a.

DOI no: 10.1073/pnas.1416515111

Proc Natl Acad Sci U S A 111:17444-17449 (2014)

PubMed id: 25385611

Structure of Crumbs tail in complex with the PALS1 PDZ-SH3-GK tandem reveals a highly specific assembly mechanism for the apical Crumbs complex.

Y.Li, Z.Wei, Y.Yan, Q.Wan, Q.Du, M.Zhang.

ABSTRACT

The Crumbs (Crb) complex, formed by Crb, PALS1, and PATJ, is evolutionarily conserved in metazoans and acts as a master cell-growth and -polarity regulator at the apical membranes in polarized epithelia. Crb intracellular functions, including its direct binding to PALS1, are mediated by Crb's highly conserved 37-residue cytoplasmic tail. However, the mechanistic basis governing the highly specific Crb-PALS1 complex formation is unclear, as reported interaction between the Crb tail (Crb-CT) and PALS1 PSD-95/DLG/ZO-1 (PDZ) domain is weak and promiscuous. Here we have discovered that the PDZ-Src homolgy 3 (SH3)-Guanylate kinase (GK) tandem of PALS1 binds to Crb-CT with a dissociation constant of 70 nM, which is ∼100-fold stronger than the PALS1 PDZ-Crb-CT interaction. The crystal structure of the PALS1 PDZ-SH3-GK-Crb-CT complex reveals that PDZ-SH3-GK forms a structural supramodule with all three domains contributing to the tight binding to Crb. Mutations disrupting the tertiary interactions of the PDZ-SH3-GK supramodule weaken the PALS1-Crb interaction and compromise PALS1-mediated polarity establishment in Madin-Darby canine kidney (MDCK) cysts. We further show that specific target binding of other members of membrane-associated guanylate kinases (MAGUKs) (e.g., CASK binding to neurexin) also requires the presence of their PDZ-SH3-GK tandems.