What are protein domains?
Protein domains are unique units within a protein that serve specific structural or functional roles, often contributing to the protein's overall function through distinct interactions or activities. These domains can be found across a range of proteins, each with different functions, highlighting their versatile nature.[1] A protein like Nck, which is part of the adaptor protein family, illustrates how proteins can contain multiple domains (including three SH3 domains and an SH2 domain) that facilitate the assembly of protein complexes through specific binding interactions.[1] Domains represent fundamental structural, functional, and evolutionary components of proteins, capable of folding independently and often sharing evolutionary homology. The identification of these domains has evolved over the years, with methods categorizable into sequence-based or structure-based approaches, providing deep insights into protein architecture and function.[2]
Fig1: Domain composition of NCK gene
Domains in SLC35A2
The SLC35A family consists of membrane proteins responsible for transporting nucleotide sugars from the cytoplasm into Golgi vesicles. Specifically, SLC35A1 is involved in the transport of CMP-sialic acid, while SLC35A2 facilitates the transport of UDP-galactose, and SLC35A3 moves UDP-GlcNAc across the membrane.[3] The SLC35A2 proteins works as integral component of golgi appratus membrane to facilitate pyrimidine nucleotide-sugar transmembrane transporter acitivity.
Nucleotide sugar transporter doamin is conserved
Conserved domains in SLC35A2 homologs were identified and visualized below using SMART and InterPro. The nucleotide sugar transporter domain is high conserved across animals, plants, and fungi, which one of the C.elegans paralogs has additional EMMA domain and Arabidopsis thaliana has a UAA domain.
Discussion
Within the SLC35A2 protein, domains play an essential role in its function as a nucleotide sugar transporter within the Golgi apparatus, illustrating the protein's involvement in glycosylation processes. The conservation of the nucleotide sugar transporter domain across various species, from animals to plants and fungi, underscores the evolutionary importance and the fundamental role of these domains in maintaining essential cellular functions. The presence of additional domains like the EMMA domain in one of the C. elegans paralogs and the UAA domain in Arabidopsis thaliana further highlights the diversity and specialization of protein domains, suggesting adaptation to species-specific functions or regulatory mechanisms.
The domain composition and conservation across species also provide valuable insights for biomedical research and biotechnology applications. For example, understanding the domain structure of SLC35A2 can inform the development of therapeutic interventions targeting glycosylation disorders. Furthermore, the conserved nature of these domains may be leveraged to create cross-species models for studying diseases, potentially accelerating the discovery of drugs and therapeutic strategies. Thus, protein domains not only offer a window into the functional capabilities of proteins but also serve as a bridge connecting evolutionary biology with translational medicine.
The domain composition and conservation across species also provide valuable insights for biomedical research and biotechnology applications. For example, understanding the domain structure of SLC35A2 can inform the development of therapeutic interventions targeting glycosylation disorders. Furthermore, the conserved nature of these domains may be leveraged to create cross-species models for studying diseases, potentially accelerating the discovery of drugs and therapeutic strategies. Thus, protein domains not only offer a window into the functional capabilities of proteins but also serve as a bridge connecting evolutionary biology with translational medicine.
Reference:
[1]Embl-Ebi. (n.d.). What are protein domains? | Protein classification. https://www.ebi.ac.uk/training/online/courses/protein-classification-intro-ebi-resources/protein-classification/what-are-protein-domains/
[2]Wang, Y., Zhang, H., Zhong, H., & Xue, Z. (2021). Protein domain identification methods and online resources. Computational and Structural Biotechnology Journal, 19, 1145–1153. https://doi.org/10.1016/j.csbj.2021.01.041
[3]Hadley, B., Maggioni, A., Ashikov, A., Day, C. J., Haselhorst, T., & Tiralongo, J. (2014). Structure and function of nucleotide sugar transporters: Current progress. Computational and Structural Biotechnology Journal, 10(16), 23–32. https://doi.org/10.1016/j.csbj.2014.05.003
Image reference:
https://www.thomasnet.com/insights/deepmind-releases-most-complete-database-of-3d-human-protein-structures/
https://www.ebi.ac.uk/training/online/courses/protein-classification-intro-ebi-resources/protein-classification/what-are-protein-domains/
[1]Embl-Ebi. (n.d.). What are protein domains? | Protein classification. https://www.ebi.ac.uk/training/online/courses/protein-classification-intro-ebi-resources/protein-classification/what-are-protein-domains/
[2]Wang, Y., Zhang, H., Zhong, H., & Xue, Z. (2021). Protein domain identification methods and online resources. Computational and Structural Biotechnology Journal, 19, 1145–1153. https://doi.org/10.1016/j.csbj.2021.01.041
[3]Hadley, B., Maggioni, A., Ashikov, A., Day, C. J., Haselhorst, T., & Tiralongo, J. (2014). Structure and function of nucleotide sugar transporters: Current progress. Computational and Structural Biotechnology Journal, 10(16), 23–32. https://doi.org/10.1016/j.csbj.2014.05.003
Image reference:
https://www.thomasnet.com/insights/deepmind-releases-most-complete-database-of-3d-human-protein-structures/
https://www.ebi.ac.uk/training/online/courses/protein-classification-intro-ebi-resources/protein-classification/what-are-protein-domains/