PDBsum entry 1x8s

Cell cycle

PDB id: 1x8s

Contents

Protein chain

98 a.a. *

Ligands

HIS-ARG-GLU-MET-ALA-VAL-ASP-CYS-PRO

Waters ×5

* Residue conservation analysis

PDB id:

1x8s

Name:

Cell cycle

Title:

Structure of the par-6 pdz domain with a pals1 internal ligand

Structure:

Cg5884-pa. Chain: a. Synonym: par-6. Engineered: yes. Pals1 peptide. Chain: b. Engineered: yes

Source:

Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: par-6. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: solid phase peptide synthesis

Biol. unit:

Hexamer (from PQS)

Resolution:

2.50Å R-factor: 0.217 R-free: 0.254

Authors:

R.R.Penkert,H.M.Divittorio,K.E.Prehoda

Key ref:

R.R.Penkert et al. (2004). Internal recognition through PDZ domain plasticity in the Par-6-Pals1 complex. Nat Struct Mol Biol, 11, 1122-1127. PubMed id: 15475968 DOI: 10.1038/nsmb839

Date:

18-Aug-04 Release date: 07-Dec-04

Protein chain

O97111  (O97111_DROME) -  LD29223p from Drosophila melanogaster

Seq: 351 a.a.

Struc: 98 a.a.

DOI no: 10.1038/nsmb839

Nat Struct Mol Biol 11:1122-1127 (2004)

PubMed id: 15475968

Internal recognition through PDZ domain plasticity in the Par-6-Pals1 complex.

R.R.Penkert, H.M.DiVittorio, K.E.Prehoda.

ABSTRACT

PDZ protein interaction domains are typically selective for C-terminal ligands, but non-C-terminal, 'internal' ligands have also been identified. The PDZ domain from the cell polarity protein Par-6 binds C-terminal ligands and an internal sequence from the protein Pals1/Stardust. The structure of the Pals1-Par-6 PDZ complex reveals that the PDZ ligand-binding site is deformed to allow for internal binding. Whereas binding of the Rho GTPase Cdc42 to a CRIB domain adjacent to the Par-6 PDZ regulates binding of C-terminal ligands, the conformational change that occurs upon binding of Pals1 renders its binding independent of Cdc42. These results suggest a mechanism by which the requirement for a C terminus can be readily bypassed by PDZ ligands and reveal a complex set of cooperative and competitive interactions in Par-6 that are likely to be important for cell polarity regulation.

Selected figure(s)

Figure 3.
Figure 3. Critical interactions in Pals1 internal PDZ binding. (a) Par-6 PDZ -C-terminal ligand interactions. The peptide-binding pocket from the C-terminal peptide -Par-6 PDZ complex (PDB entry 1RZX) is shown. Peptide residues are labeled by amino acid and PDZ domain residues are labeled by amino acid and sequence number. The distance between the C terminus and Lys165 is shown (solid line) along with interactions between the carboxylate and the PDZ backbone (dashed lines). (b) Par-6 PDZ -Pals1 internal ligand interactions. The interactions between the PDZ domain and peptide are shown as in a.

Figure 5.
Figure 5. Modes of PDZ C-terminal and internal recognition. In PDZ C-terminal ligand recognition, the carboxylate-binding loop enforces C-terminal binding by preventing extension past the P(0) residue. In the -finger internal PDZ recognition mode of recognition, used by nNOS-syntrophin7 and presumably disulfide-containing ligands8, a sharp turn in the ligand allows it to bypass the steric requirement imposed by the carboxylate-binding loop. The Pals1 -Par-6 PDZ interaction represents a new type of internal interaction in which the carboxylate-binding loop is deformed to allow for extension past the P(0) residue. An interaction with the P(+1) residue is critical for this mode of recognition.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2004, 11, 1122-1127) copyright 2004.

Figures were selected by the author.