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

The crystal structure of Cwp84, an S-layer protein from Clostridium difficile is presented for the first time. The cathepsin L-like fold of cysteine protease domain, a newly observed ‘lectin-like’ domain and several other features are described. 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 rolemore » in the C. difficile S-layer maturation mechanism.« less
Authors:
 [1] ;  [2] ;  [3] ;  [1] ; ;  [1] ;  [2] ; ;  [3] ;  [1]
  1. University of Bath, Claverton Down, Bath BA2 7AY (United Kingdom)
  2. (United Kingdom)
  3. Public Health England, Porton Down, Salisbury SP4 0JG (United Kingdom)
Publication Date:
OSTI Identifier:
22347772
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section D: Biological Crystallography; Journal Volume: 70; Journal Issue: Pt 7; Other Information: PMCID: PMC4089489; PMID: 25004975; PUBLISHER-ID: wa5073; OAI: oai:pubmedcentral.nih.gov:4089489; Copyright (c) Bradshaw et al. 2014; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; CALCIUM IONS; CLEAVAGE; CRYSTAL STRUCTURE; CRYSTALS; CYSTEINE; LAYERS; MOLECULAR WEIGHT; RESOLUTION; SURFACES