PROSITE documentation PDOC51170

Cell wall-binding repeat profile

The cell wall-binding repeat (CW) is a ~20 amino acid residue module essentially found in two bacterial Gram-positive protein families: choline binding proteins and glucosyltransferases (EC 2.4.1.5). In choline-binding proteins cell wall binding repeats bind to choline moieties of both teichoic and lipoteichoic acids, two components peculiar to the cell surface of Gram-positive bacteria [1,2]. In glucosyltransferases the region spanning the CW repeats is a glucan binding domain [3].

Several crystal structures of CW have been solved [4,5]. In the choline binding protein LytA (see <PDB:1HCX>), the repeats adopt a solenoid fold consisting exclusively of β-hairpins that stack to form a left-handed superhelix with a boomerang-like shape. The choline groups bind between β-hairpin 'steps' of the superhelix [4]. In Cpl-1 CW repeats assemble in two sub-domains: an N-terminal superhelical moiety similar to the LytA one and a C-terminal β-sheet involved in interactions with the lysozyme domain. Choline is bound between repeats 1 and 2, and, 2 and 3 of the superhelical sub-domain [5].

Some proteins known to contain cell-wall binding repeats:

• Pneumococcal N-acetylmuramoyl-L-alanine amidase (autolysin, lytA) (EC 3.5.1.28). It is a surface-exposed enzyme that rules the self-destruction of pneumococcal cells through degradation of their peptidoglycan backbone. It mediates the release of toxic substances that damage the host tissues.
• Pneumococcal endo-β-N-acetylglucosaminidase (lytB) (EC 3.2.1.96). It plays an important role in cell wall degradation and cell separation
• Pneumococcal teichoic acid phosphorylcholine esterase (pce or cbpE), a cell wall hydrolase important for cellular adhesion and colonisation.
• Lactobacillales glucosyltransferase. It catalyzes the transfer of glucosyl units from the cleavage of sucrose to a growing chain of glucan.
• Clostridium difficile toxin A (tcdA) and toxin B (tcdb). They are the causative agents of the antibiotic-associated pseudomembranous colitis. They are intracellular acting toxins that reach their targets after receptor-mediated endocytosis.
• Clostridium acetobutylicum cspA protein.
• Siphoviridae bacteriophages N-acetylmuramoyl-L-alanine amidase. It lyses the bacterial host cell wall.
• Podoviridae lysozyme protein (cpl-1). It is capable of digesting the pneumococcal cell wall.

The profile we developed covers the 20 amino acids of the CW repeat.