2LUI

Structure of the PICK PDZ domain in complex with the DAT C-terminal

2LUI の概要

• エントリーDOI: 10.2210/pdb2lui/pdb
• NMR情報: BMRB: 18522
• 分子名称: PICK1 PDZ DOMAIN FUSED TO THE C10 DAT LIGAND (1 entity in total)
• 機能のキーワード: pdz, dat c-terminal, pick1, protein binding
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12428.33

構造登録者

Erlendsson, S.,Rathje, M.,Heidarsson, P.O.,Poulsen, F.M.,Madsen, K.L.,Teilum, K.,Gether, U. (登録日: 2012-06-14, 公開日: 2013-06-19, 最終更新日: 2024-05-01)

主引用文献

Erlendsson, S.,Rathje, M.,Heidarsson, P.O.,Poulsen, F.M.,Madsen, K.L.,Teilum, K.,Gether, U.
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, 2014

PubMed 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.

PubMed: 25023278
DOI: 10.1074/jbc.M114.548743

実験手法

SOLUTION NMR