4CI7

The crystal structure of the cysteine protease and lectin-like domains of Cwp84, a surface layer associated protein of Clostridium difficile

Summary for 4CI7

• Entry DOI: 10.2210/pdb4ci7/pdb
• Descriptor: CELL SURFACE PROTEIN (PUTATIVE CELL SURFACE-ASSOCIATED CYSTEINE PROTEASE), SULFATE ION, GLYCEROL, ... (6 entities in total)
• Functional Keywords: hydrolase, s-layer, cwp, cell wall protein, surface protein
• Biological source: CLOSTRIDIUM DIFFICILE
• Total number of polymer chains: 2
• Total formula weight: 106303.40

Authors

Bradshaw, W.J.,Kirby, J.M.,Thiyagarajan, N.,Chambers, C.J.,Davies, A.H.,Roberts, A.K.,Shone, C.C.,Acharya, K.R. (deposition date: 2013-12-06, release date: 2014-05-14, Last modification date: 2024-05-08)

Primary citation

Bradshaw, W.J.,Kirby, J.M.,Thiyagarajan, N.,Chambers, C.J.,Davies, A.H.,Roberts, A.K.,Shone, C.C.,Acharya, K.R.
The Structure of the Cysteine Protease and Lectin-Like Domains of Cwp84, a Surface Layer-Associated Protein from Clostridium Difficile
Acta Crystallogr.,Sect.D, 70:1983-, 2014

PubMed Abstract: 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 Å 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.

PubMed: 25004975
DOI: 10.1107/S1399004714009997

Experimental method

X-RAY DIFFRACTION (1.4 Å)