SecretEPDB: a comprehensive web-based resource for secreted effector proteins of the bacterial types III, IV and VI secretion systems

Abstract

Bacteria translocate effector molecules to host cells through highly evolved secretion systems. By definition, the function of these effector proteins is to manipulate host cell biology and the sequence, structural and functional annotations of these effector proteins will provide a better understanding of how bacterial secretion systems promote bacterial survival and virulence. Here we developed a knowledgebase, termed SecretEPDB (Bacterial Secreted Effector Protein DataBase), for effector proteins of type III secretion system (T3SS), type IV secretion system (T4SS) and type VI secretion system (T6SS). SecretEPDB provides enriched annotations of the aforementioned three classes of effector proteins by manually extracting and integrating structural and functional information from currently available databases and the literature. The database is conservative and strictly curated to ensure that every effector protein entry is supported by experimental evidence that demonstrates it is secreted by a T3SS, T4SS or T6SS. The annotations of effector proteins documented in SecretEPDB are provided in terms of protein characteristics, protein function, protein secondary structure, Pfam domains, metabolic pathway and evolutionary details. It is our hope that this integrated knowledgebase will serve as a useful resource for biological investigation and the generation of new hypotheses for research efforts aimed at bacterial secretion systems.

Figure 1. Flowchart of the data collection process in SecretEPDB.

Figure 2. Statistical summary of collected entries currently in SecretEPDB.

(A) Distribution of effector protein entries according to the original resources used; (B) Distribution of entries from UniProt and NCBI protein database.

Figure 3. Distribution of collected entries according to bacterial species.

(A) Distribution of the entries from the three dominant bacterial species; (B) Statistical analysis of the entries from the top eight bacterial species.

Figure 4. Sequence logos showing the amino acid conservation and preference in T4SEs.

Sequence Logo plots of the indicated number of residues in the N-terminal (A) and C-terminal (B) regions of the collected sequences of T4SEs from Legionella pneumophila. The x-axis represents residue numbers, and Amino acids above the x-axis are favoured while those underneath the x-axis are disfavoured at the corresponding positions. Note that because of the mechanism of protein synthesis, the N-terminal position of a bacterial protein can only ever be methionine (M), isoleucine (I) or leucine (L), with M being vastly the most common.

Figure 5. Examples of search options available in SecretEPDB.

(A) Search option with UniProt ID or SecretEPDB ID; (B) Search option with a number of keywords, including protein name, mutation and species.

Figure 6. Output of the sample search against SecretEPDB using UniProt ID “Q7CQD4” as the query.

The results are displayed and organized by different annotation categories, including protein detailed information, sequence alignment, protein structure, multiple sequence alignments, Pfam domain, disorder region prediction, disorder picture, protein mutation and metabolic/signaling pathway.