PDBsum entry 2lui

Protein binding

PDB id: 2lui

Contents

Protein chain

116 a.a.

PDB id:

2lui

Name:

Protein binding

Title:

Structure of the pick pdz domain in complex with the dat c-terminal

Structure:

Pick1 pdz domain fused to the c10 dat ligand. Chain: a. Synonym: protein interacting with c kinase 1, protein kinasE C-alpha- binding protein. Engineered: yes

Source:

Rattus norvegicus. Brown rat,rat,rats. Organism_taxid: 10116. Gene: pick1, prkcabp. Expressed in: escherichia coli. Expression_system_taxid: 511693.

NMR struc:

20 models

Authors:

S.Erlendsson,M.Rathje,P.O.Heidarsson,F.M.Poulsen,K.L.Madsen,K.Teilum, U.Gether

Key ref:

S.Erlendsson et al. (2014). Protein interacting with C-kinase 1 (PICK1) binding promiscuity relies on unconventional PSD-95/discs-large/ZO-1 homology (PDZ) binding modes for nonclass II PDZ ligands. J Biol Chem, 289, 25327-25340. PubMed id: 25023278 DOI: 10.1074/jbc.M114.548743

Date:

14-Jun-12 Release date: 19-Jun-13

Protein chain

Q9EP80  (PICK1_RAT) -  PRKCA-binding protein from Rattus norvegicus

Seq: 416 a.a.

Struc: 116 a.a.*

* PDB and UniProt seqs differ at 20 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M114.548743

J Biol Chem 289:25327-25340 (2014)

PubMed id: 25023278

Protein interacting with C-kinase 1 (PICK1) binding promiscuity relies on unconventional PSD-95/discs-large/ZO-1 homology (PDZ) binding modes for nonclass II PDZ ligands.

S.Erlendsson, M.Rathje, P.O.Heidarsson, F.M.Poulsen, K.L.Madsen, K.Teilum, U.Gether.

ABSTRACT

PDZ domain proteins control multiple cellular functions by governing assembly of protein complexes. It remains unknown why individual PDZ domains can bind the extreme C terminus of very diverse binding partners and maintain selectivity. By employing NMR spectroscopy, together with molecular modeling, mutational analysis, and fluorescent polarization binding experiments, we identify here three structural mechanisms explaining why the PDZ domain of PICK1 selectively binds >30 receptors, transporters, and kinases. Class II ligands, including the dopamine transporter, adopt a canonical binding mode with promiscuity obtained via differential packing in the binding groove. Class I ligands, such as protein kinase Cα, depend on residues upstream from the canonical binding sequence that are likely to interact with flexible loop residues of the PDZ domain. Finally, we obtain evidence that the unconventional ligand ASIC1a has a dual binding mode involving a canonical insertion and a noncanonical internal insertion with the two C-terminal residues forming interactions outside the groove. Together with an evolutionary analysis, the data show how unconventional binding modes might evolve for a protein recognition domain to expand the repertoire of functionally important interactions.