PDBsum entry 2v1w

Structural protein

PDB id: 2v1w

Contents

Protein chains

89 a.a. *

Ligands

EDO

1PE

Metals

_MG

Waters ×145

* Residue conservation analysis

PDB id:

2v1w

Name:

Structural protein

Title:

Crystal structure of human lim protein ril (pdlim4) pdz domain bound to thE C-terminal peptide of human alpha-actinin-1

Structure:

Pdz and lim domain protein 4. Chain: a, b. Fragment: pdz domain, residues 1-85. Synonym: pdlim4, lim protein ril, reversion-induced lim protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: r3-prare2.

Resolution:

1.90Å R-factor: 0.174 R-free: 0.211

Authors:

M.Soundararajan,L.Shrestha,A.C.W.Pike,E.Salah,N.Burgess-Brown, J.Elkins,C.Umeano,E.Ugochukwu,F.Von Delft,C.H.Arrowsmith,A.Edwards, J.Weigelt,M.Sundstrom,D.Doyle

Key ref:

J.M.Elkins et al. (2010). Unusual binding interactions in PDZ domain crystal structures help explain binding mechanisms. Protein Sci, 19, 731-741. PubMed id: 20120020

Date:

30-May-07 Release date: 12-Jun-07

Protein chains

P50479  (PDLI4_HUMAN) -  PDZ and LIM domain protein 4 from Homo sapiens

Seq: 330 a.a.

Struc: 89 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Protein Sci 19:731-741 (2010)

PubMed id: 20120020

Unusual binding interactions in PDZ domain crystal structures help explain binding mechanisms.

J.M.Elkins, C.Gileadi, L.Shrestha, C.Phillips, J.Wang, J.R.Muniz, D.A.Doyle.

ABSTRACT

PDZ domains most commonly bind the C-terminus of their protein targets. Typically the C-terminal four residues of the protein target are considered as the binding motif, particularly the C-terminal residue (P0) and third-last residue (P-2) that form the major contacts with the PDZ domain's "binding groove". We solved crystal structures of seven human PDZ domains, including five of the seven PDLIM family members. The structures of GRASP, PDLIM2, PDLIM5, and PDLIM7 show a binding mode with only the C-terminal P0 residue bound in the binding groove. Importantly, in some cases, the P-2 residue formed interactions outside of the binding groove, providing insight into the influence of residues remote from the binding groove on selectivity. In the GRASP structure, we observed both canonical and noncanonical binding in the two molecules present in the asymmetric unit making a direct comparison of these binding modes possible. In addition, structures of the PDZ domains from PDLIM1 and PDLIM4 also presented here allow comparison with canonical binding for the PDLIM PDZ domain family. Although influenced by crystal packing arrangements, the structures nevertheless show that changes in the positions of PDZ domain side-chains and the alpha B helix allow noncanonical binding interactions. These interactions may be indicative of intermediate states between unbound and fully bound PDZ domain and target protein. The noncanonical "perpendicular" binding observed potentially represents the general form of a kinetic intermediate. Comparison with canonical binding suggests that the rearrangement during binding involves both the PDZ domain and its ligand.