Journal article
Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition
International Review of Cell and Molecular Biology, Vol.343, pp.129-218
International Review of Cell and Molecular Biology
01/01/2019
DOI: 10.1016/bs.ircmb.2018.05.013
PMCID: PMC7185565
PMID: 30712672
Abstract
Post-synaptic density-95, disks-large and zonula occludens-1 (PDZ) domains are small globular protein-protein interaction domains widely conserved from yeast to humans. They are composed of similar to 90 amino acids and form a classical two alpha-helical/six beta-strand structure. The prototypical ligand is the C-terminus of partner proteins; however, they also bind internal peptide sequences. Recent findings indicate that PDZ domains also bind phosphatidylinositides and cholesterol. Through their ligand interactions, PDZ domain proteins are critical for cellular trafficking and the surface retention of various ion channels. In addition, PDZ proteins are essential for neuronal signaling, memory, and learning. PDZ proteins also contribute to cytoskeletal dynamics by mediating interactions critical for maintaining cell-cell junctions, cell polarity, and cell migration. Given their important biological roles, it is not surprising that their dysfunction can lead to multiple disease states. As such, PDZ domain-containing proteins have emerged as potential targets for the development of small molecular inhibitors as therapeutic agents. Recent data suggest that the critical binding function of PDZ domains in cell signaling is more than just glue, and their binding function can be regulated by phosphorylation or allosterically by other binding partners. These studies also provide a wealth of structural and biophysical data that are beginning to reveal the physical features that endow this small modular domain with a central role in cell signaling.
Details
- Title: Subtitle
- Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition
- Creators
- Xu Liu - University of IowaErnesto J. Fuentes - University of Iowa
- Contributors
- L Galluzzi (Editor)
- Resource Type
- Journal article
- Publication Details
- International Review of Cell and Molecular Biology, Vol.343, pp.129-218
- Publisher
- Elsevier; LONDON
- Series
- International Review of Cell and Molecular Biology
- DOI
- 10.1016/bs.ircmb.2018.05.013
- PMID
- 30712672
- PMCID
- PMC7185565
- eISSN
- 1937-6448
- ISSN
- 1937-6448
- Number of pages
- 90
- Grant note
- P30CA022453 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 01/01/2019
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984293089102771
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