Abstract
An increasing number of surface‐associated proteins identified in Gram‐positive bacteria are characterized by intramolecular cross‐links in structurally conserved thioester, isopeptide, and ester domains (TIE proteins). Two classes of thioester domains (TEDs) have been predicted based on sequence with, to date, only representatives of Class I structurally characterized. Here, we present crystal structures of three Class II TEDs from Bacillus anthracis, vancomycin‐resistant Staphylococcus aureus, and vancomycin‐resistant Enterococcus faecium. These proteins are structurally distinct from Class I TEDs due to a β‐sandwich domain that is inserted into the conserved TED fold to form a slipknot structure. Further, the B. anthracis TED domain is presented in the context of a full‐length sortase‐anchored protein structure (BaTIE). This provides insight into the three‐dimensional arrangement of TIE proteins, which emerge as very abundant putative adhesins of Gram‐positive bacteria.
Highlights
Adhesion of microbes to target molecules is a critical step in colonization and maintenance of infection
BaTIE was among the first surface proteins from B. anthracis described, and has previously been studied as BasC and BA5258.9–12 It has been suggested to function as a collagen-binding protein.[9]
Sequence similarity searches suggest that thioester domains (TEDs) and TIE proteins are extremely abundant, and very diverse with respect to their domain composition and sequences
Summary
Adhesion of microbes to target molecules is a critical step in colonization and maintenance of infection. Gln side-chains and first identified in the second thioester domain (TED) of the Streptococcus pyogenes minor pilin Cpa,[3] play a negligible role in protein stability,[4] but are suggested to mediate covalent. We describe three-dimensional structures of a new class of bacterial proteins that may function by chemically reacting with binding partners. This work highlights a large, highly conserved, structural class of surface-exposed proteins with unknown function. It may contribute to the development of novel anti-adhesive strategies for the prevention and treatment of bacterial infections
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