4ci7

Publication Abstract from PubMed

Clostridium difficile is a major problem as an aetiological agent for antibiotic-associated diarrhoea. The mechanism by which the bacterium colonizes the gut during infection is poorly understood, but undoubtedly involves a myriad of components present on the bacterial surface. The mechanism of C. difficile surface-layer (S-layer) biogenesis is also largely unknown but involves the post-translational cleavage of a single polypeptide (surface-layer protein A; SlpA) into low- and high-molecular-weight subunits by Cwp84, a surface-located cysteine protease. Here, the first crystal structure of the surface protein Cwp84 is described at 1.4 A resolution and the key structural components are identified. The truncated Cwp84 active-site mutant (amino-acid residues 33-497; C116A) exhibits three regions: a cleavable propeptide and a cysteine protease domain which exhibits a cathepsin L-like fold followed by a newly identified putative carbohydrate-binding domain with a bound calcium ion, which is referred to here as a lectin-like domain. This study thus provides the first structural insights into Cwp84 and a strong base to elucidate its role in the C. difficile S-layer maturation mechanism.

The structure of the cysteine protease and lectin-like domains of Cwp84, a surface layer-associated protein from Clostridium difficile.,Bradshaw WJ, Kirby JM, Thiyagarajan N, Chambers CJ, Davies AH, Roberts AK, Shone CC, Acharya KR Acta Crystallogr D Biol Crystallogr. 2014 Jul 1;70(Pt 7):1983-93. doi:, 10.1107/S1399004714009997. Epub 2014 Jun 29. PMID:25004975^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.