The binding affinities of proteins interacting with the PDZ domain of PICK1

Ashini Bolia, Z. Nevin Gerek, Ozlem Keskin, Sefika Ozkan, Kumlesh K. Dev

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Protein interacting with C kinase (PICK1) is well conserved throughout evolution and plays a critical role in synaptic plasticity by regulating the trafficking and posttranslational modification of its interacting proteins. PICK1 contains a single PSD95/DlgA/Zo-1 (PDZ) protein-protein interaction domain, which is promiscuous and shown to interact with over 60 proteins, most of which play roles in neuronal function. Several reports have suggested the role of PICK1 in disorders such as epilepsy, pain, brain trauma and stroke, drug abuse and dependence, schizophrenia and psychosis. Importantly, lead compounds that block PICK1 interactions are also now becoming available. Here, a new modeling approach was developed to investigate binding affinities of PDZ interactions. Using these methods, the binding affinities of all major PICK1 interacting proteins are reported and the effects of PICK1 mutations on these interactions are described. These modeling methods have important implications in defining the binding properties of proteins interacting with PICK1 as well as the general structural requirements of PDZ interactions. The study also provides modeling methods to support in the drug design of ligands for PDZ domains, which may further aid in development of the family of PDZ domains as a drug target.

Original languageEnglish (US)
Pages (from-to)1393-1408
Number of pages16
JournalProteins: Structure, Function and Bioinformatics
Volume80
Issue number5
DOIs
StatePublished - May 2012

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Carrier Proteins
Substance-Related Disorders
Proteins
Substance-Induced Psychoses
Pharmaceutical Preparations
Protein Interaction Domains and Motifs
Lead compounds
Neuronal Plasticity
Drug Design
Post Translational Protein Processing
Plasticity
Epilepsy
Brain
Schizophrenia
Phosphotransferases
Stroke
Ligands
Pain
Mutation

Keywords

  • Binding affinity
  • Modeling
  • Molecular docking
  • PICK1

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Molecular Biology

Cite this

The binding affinities of proteins interacting with the PDZ domain of PICK1. / Bolia, Ashini; Gerek, Z. Nevin; Keskin, Ozlem; Ozkan, Sefika; Dev, Kumlesh K.

In: Proteins: Structure, Function and Bioinformatics, Vol. 80, No. 5, 05.2012, p. 1393-1408.

Research output: Contribution to journalArticle

Bolia, Ashini ; Gerek, Z. Nevin ; Keskin, Ozlem ; Ozkan, Sefika ; Dev, Kumlesh K. / The binding affinities of proteins interacting with the PDZ domain of PICK1. In: Proteins: Structure, Function and Bioinformatics. 2012 ; Vol. 80, No. 5. pp. 1393-1408.
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