Ligand-dependent dynamics and intramolecular signaling in a PDZ domain

Ernesto J Fuentes; Channing J Der; Andrew L Lee

doi:10.1016/j.jmb.2003.11.010

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Ligand-dependent dynamics and intramolecular signaling in a PDZ domain

Journal article

Peer reviewed

Ligand-dependent dynamics and intramolecular signaling in a PDZ domain

Ernesto J Fuentes, Channing J Der and Andrew L Lee

Journal of molecular biology, Vol.335(4), pp.1105-1115

01/23/2004

DOI: 10.1016/j.jmb.2003.11.010

PMID: 14698303

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Abstract

Allosteric communication is a fundamental process that proteins use to propagate signals from one site to functionally important distal sites. Although allostery is usually associated with multimeric proteins and enzymes, "long-range" communication may be a fundamental property of proteins. In some cases, communication occurs with minimal structural change. PDZ (post-synaptic density-95/discs large/zonula occludens-1) domains are small, protein-protein binding modules that can use multiple surfaces for docking diverse molecules. Furthermore, these domains have long-range energetic couplings that link the ligand-binding site to distal regions of the structure. Here, we show that allosteric behavior in a representative member of the PDZ domain family may be directly detected using side-chain methyl dynamics measurements. The changes in side-chain dynamics parameters in the second PDZ domain from the human tyrosine phosphatase 1E (hPTP1E) were determined upon binding a peptide target. Long-range dynamic effects were detected that correspond to previously observed pair-wise energetic couplings. These results provide one of the first experimental examples for the potential role of ps-ns timescale dynamics in propagating long-range signals within a protein, and reinforce the idea that dynamic fluctuations in proteins contribute to allosteric signal transduction.

Protein Structure, Tertiary

Amino Acid Sequence

Peptides - chemistry

Signal Transduction

Allosteric Regulation

Humans

Models, Molecular

Molecular Sequence Data

Protein Tyrosine Phosphatases - metabolism

Amino Acid Motifs

Thermodynamics

Protein Tyrosine Phosphatases - chemistry

Animals

Peptides - metabolism

Protein Binding

Ligands

Mice

Binding Sites

Details

Title: Subtitle: Ligand-dependent dynamics and intramolecular signaling in a PDZ domain
Creators: Ernesto J Fuentes - Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Channing J Der
Andrew L Lee
Resource Type: Journal article
Publication Details: Journal of molecular biology, Vol.335(4), pp.1105-1115
Publisher: England
DOI: 10.1016/j.jmb.2003.11.010
PMID: 14698303
ISSN: 0022-2836
eISSN: 1089-8638
Language: English
Date published: 01/23/2004
Academic Unit: Biochemistry and Molecular Biology
Record Identifier: 9984024542602771

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