The origin of the PDZ domain revealed: How do these three proteins change our understanding of cellular structure?

The PDZ domain is a ubiquitous structural protein domain, usually consisting of 80 to 90 amino acids, found in signaling proteins of bacteria, yeast, plants, viruses and animals. These PDZ domain-containing proteins play a key role in the localization of membraneless receptors to cytoskeletal components. PDZ domains help organize signaling complexes and form and maintain these complexes on cell membranes. The PDZ domain is also a crucial component in the cell signal transduction process.

PDZ is composed of the first letters of the names of the three earliest discovered proteins: postsynaptic density protein 95 (PSD95), Drosophila large plate tumor suppressor (Dlg1) and interface membrane protein 1 (ZO- 1).

The functions of PDZ domains are not limited to connecting membrane receptor proteins with cytoskeletal components. They also play an important role in the regulation of multiple cell signaling pathways. This makes proteins containing PDZ domains indispensable in the coordination of cellular functions and message transmission. This article will provide an in-depth exploration of the origin, structure, and function of the PDZ domain and its impact on the understanding of cell structure.

Origin of discovery

The name of the PDZ domain comes from the three proteins for which this domain was first discovered. Scientists have identified hundreds of PDZ domains since they were first identified more than 20 years ago. In fact, the first mention of the PDZ domain was not in a formal scientific paper, but in a letter of assurance. In September 1995, Dr. Mary B. Kennedy of Caltech published a correction in which she refuted the name given to a newly discovered protein domain by another group of scientists and proposed the PDZ domain Named to better reflect its origin and distribution.

Structure of PDZ domain

The structure of the PDZ domain is conserved in different proteins. Generally, PDZ domains contain 5 to 6 β-strands and one short and one long α-helix. This gives the PDZ domain a spherical shape with a diameter of approximately 35 Å. The PDZ domain mainly binds to the C-terminal short region of other specific proteins and connects through the reinforcement of the β chain, which means that the β chain of the PDZ domain will extend to receive the unique β chain from the partner protein.

Function of PDZ domain

The two main functions of the PDZ domain are to localize cellular components and regulate cellular pathways. The first discovered function of the PDZ domain was to anchor membrane receptor proteins to the cytoskeleton. Proteins with PDZ domains can flexibly interact with a variety of cellular components to exert various cell regulatory functions.

The PDZ domain is basically responsible for positioning structural elements inside cells and regulating different signaling pathways. Only when the components within the cell are positioned correctly can the cell function properly.

Location of cellular components

PDZ domains play a crucial role in the positioning of cellular components, helping to maintain complex scaffold structures. Particularly in nerve cells, the PDZ domain ensures that specific receptors required for the activity of neurotransmitters are in the correct location, which is crucial for the transmission of signals. Without this interaction, receptors would diffuse across the synapse due to the fluidity of the lipid membrane.

Regulatory effect

In addition to localization, PDZ domains are also involved in the regulation of different cellular pathways. For example, PDZ domains can enhance signal transmission by colocalizing with signaling molecules. This mechanism is particularly evident in PDZ-based protein interactions.

Activity regulation of PDZ domain

The activity of PDZ domains can be modulated through multiple mechanisms, including allosteric interactions and post-translational modifications. Post-translational modifications, especially phosphorylation, often inhibit the function of the PDZ domain and change its binding mode with ligands, thereby affecting cell signaling.

PDZ protein

PDZ proteins are a family of proteins containing PDZ domains that are widely present in eukaryotes and bacteria. These PDZ proteins often bind to other protein domains to exert their specific functions. The three most well-known PDZ proteins are PSD-95, GRIP and HOMER, which have different functions in different cell signaling processes.

Conclusion

The existence and function of the PDZ domain not only changed our understanding of cell structure, but also triggered further research and promoted the understanding of different diseases. With the advancement of science and technology, we will have a deeper understanding of the role of the PDZ domain in health and pathological conditions, which is of great significance for potential treatment strategies in the future. So, how will these cellular processes affected by PDZ domains lead us toward new biomedical breakthroughs?

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