Abstract
Type III secretion system (T3SS) plays important roles in bacteria and host cell interactions by specifically translocating type III effectors into the cytoplasm of the host cells. The N-terminal amino acid sequences of the bacterial type III effectors determine their specific secretion via type III secretion conduits. It is still unclear as to how the N-terminal sequences guide this specificity. In this work, the amino acid composition, secondary structure, and solvent accessibility in the N-termini of type III and non-type III secreted proteins were compared and contrasted. A high-efficacy mathematical model based on these joint features was developed to distinguish the type III proteins from the non-type III ones. The results indicate that secondary structure and solvent accessibility may make important contribution to the specific recognition of type III secretion signals. Analysis also showed that the joint feature of the N-terminal 6th–10th amino acids are especially important for guiding specific type III secretion. Furthermore, a genome-wide screening was performed to predict Salmonella type III secreted proteins, and 8 new candidates were experimentally validated. Interestingly, type III secretion signals were also predicted in gram-positive bacteria and yeasts. Experimental validation showed that two candidates from yeast can indeed be secreted through Salmonella type III secretion conduit. This research provides the first line of direct evidence that secondary structure and solvent accessibility contain important features for guiding specific type III secretion. The new software based on these joint features ensures a high accuracy (general cross-validation sensitivity of ∼96% at a specificity of ∼98%) in silico identification of new type III secreted proteins, which may facilitate our understanding about the specificity of type III secretion and the evolution of type III secreted proteins.
Highlights
Bacteria encode different protein translocation systems, via which various bacterial substrate proteins are translocated into the host cells in order to function in pathogenesis or symbiosis [1,2,3]
We further explore the possible contribution of secondary structure and solvent accessibility to the specific T3S recognition
The resulting non-redundant and reliable dataset was subjected to position-specific amino acid composition (Aac), secondary structure (Sse) and accessibility states (Acc) profile analysis
Summary
Bacteria encode different protein translocation systems, via which various bacterial substrate proteins are translocated into the host cells in order to function in pathogenesis or symbiosis [1,2,3]. After entering the host cell cytoplasm, these effectors can interact with the host proteins and mediate bacterial infection or invasion Due to their importance in bacteria-host interaction, identification of new T3S effectors has attracted much research attention in the past decade. Possibly due to bacterial adaptation to different hosts or environments, the number of T3S effectors varies greatly among different bacterial species, and the sequences lack apparent similarity among different effectors [1,2,3]. This makes it extremely difficult to identify new T3S effectors by sequence alignment or phylogenetic approaches. Other general properties, such as distinct G+C nucleotide content, clustering with chaperones, transcriptional co-regulation with apparatus genes, etc., were used for screening new effectors that scatter in the genomes [14,15,16]
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