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- W4313374487 abstract "Abstract Toll-Interleukin-1R Resistance (TIR) domains represent a type of protein fold ubiquitously present in all forms of cellular life. The TIR domains are present in functionally and architecturally diverse proteins. A large subgroup of metazoan TIRs is involved in signaling that initiate and regulate the immune response elicited by infection or damaged self. This study applies Bayesian partitioning with pattern selection (BPPS) to classify the TIR domains based on sequence patterns that best distinguish individual groups. The algorithm was applied to >26000 phylogenetically diverse TIR domain sequences selected for non-redundancy from publicly available protein sequence banks. The analysis has revealed 10 metazoan groups, nine of which comprise either orthologous proteins or a protein family. Available structural data suggest that the identified groups may be uniquely characterized by regional backbone fold variants, which can be associated with a corresponding group-specific sequence motif. In addition to these fold-defining motifs, the BPPS also identified groups of surface-exposed residues conserved in TIRAP and MyD88 orthologs, which correspond to predicted sites that mediate the signal-dependent TIR oligomerization. This analysis also has clarified the functional significance of locally conserved sequence motifs, named Box 2 and Box 3, as each of these motifs is a part of a larger block of conserved, intramolecularly interacting residues. Finally, this study has identified the sequence patterns that differentiate TIRs of different classes, such TIRs of TLRs, from TIRs of the IL-1R family, or their adapter proteins, and highlights the differences between metazoan, plant, and bacterial TIRs." @default.
- W4313374487 created "2023-01-06" @default.
- W4313374487 creator A5010571747 @default.
- W4313374487 creator A5071156187 @default.
- W4313374487 date "2020-05-01" @default.
- W4313374487 modified "2023-09-27" @default.
- W4313374487 title "Evolutionary conserved sequence patterns that determine functional specialization of metazoan TIR domains" @default.
- W4313374487 doi "https://doi.org/10.4049/jimmunol.204.supp.79.7" @default.
- W4313374487 hasPublicationYear "2020" @default.
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