title: Cwp84, a Clostridium difficile cysteine protease, exhibits conformational flexibility in the absence of its propeptide.
abstract: In recent decades, the global healthcare problems caused by Clostridium difficile have increased at an alarming rate. A greater understanding of this antibiotic-resistant bacterium, particularly with respect to how it interacts with the host, is required for the development of novel strategies for fighting C. difficile infections. The surface layer (S-layer) of C. difficile is likely to be of significant importance to host-pathogen interactions. The mature S-layer is formed by a proteinaceous array consisting of multiple copies of a high-molecular-weight and a low-molecular-weight S-layer protein. These components result from the cleavage of SlpA by Cwp84, a cysteine protease. The structure of a truncated Cwp84 active-site mutant has recently been reported and the key features have been identified, providing the first structural insights into the role of Cwp84 in the formation of the S-layer. Here, two structures of Cwp84 after propeptide cleavage are presented and the three conformational changes that are observed are discussed. These changes result in a reconfiguration of the active site and exposure of the hydrophobic pocket.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, England.
authors.forename: William J
authors.initials: WJ
authors.lastname: Bradshaw
authors.affiliation: Public Health England, Porton Down, Salisbury SP4 0JG, England.
authors.forename: April K
authors.initials: AK
authors.lastname: Roberts
authors.affiliation: Public Health England, Porton Down, Salisbury SP4 0JG, England.
authors.forename: Clifford C
authors.initials: CC
authors.lastname: Shone
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, England.
authors.forename: K Ravi
authors.initials: KR
authors.lastname: Acharya
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D016360:Clostridioides difficile / Q000201:enzymology*; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011498:Protein Precursors / Q000737:chemistry*; D059748:Proteolysis
chemical_list: D001426:Bacterial Proteins; D011498:Protein Precursors; C524258:Cwp84 protein, Clostridium difficile; D003546:Cysteine Endopeptidases
keywords: Clostridium difficile; Cwp84; host–pathogen interactions; surface layer