8T3I

Crystal structure of mutant exfoliative toxin C (ExhC) from Mammaliicoccus sciuri

Summary for 8T3I

• Entry DOI: 10.2210/pdb8t3i/pdb
• Descriptor: Exfoliative toxin C (2 entities in total)
• Functional Keywords: peptidase, necrotic activity, toxin
• Biological source: Mammaliicoccus sciuri
• Total number of polymer chains: 2
• Total formula weight: 56897.15

Authors

Gismene, C.,Calil, F.A.,Hernandez Gonzalez, J.E.,Ziem Nascimento, A.F.,Santisteban, A.R.N.,Arni, R.K.,Barros Mariutti, R. (deposition date: 2023-06-07, release date: 2023-11-08, Last modification date: 2024-02-14)

Primary citation

Gismene, C.,Gonzalez, J.E.H.,de Freitas Calmon, M.,Nascimento, A.F.Z.,Santisteban, A.R.N.,Calil, F.A.,da Silva, A.D.T.,Rahal, P.,Goes, R.M.,Arni, R.K.,Mariutti, R.B.
Necrotic activity of ExhC from Mammaliicoccus sciuri is mediated by specific amino acid residues.
Int.J.Biol.Macromol., 254:127741-127741, 2024

PubMed Abstract: Mammaliicoccus sciuri, a commensal and pathogenic bacterium of significant clinical and veterinary relevance, expresses exfoliative toxin C (ExhC), a specific glutamyl endopeptidase belonging to the chymotrypsin family as the principal virulence factor. However, unlike most members of this family, ETs are inactive against a wide range of substrates and possess exquisite specificity for desmoglein-1 (Dsg1), a cadherin-like adhesion molecule that is crucial to maintain tissue integrity, thereby preventing the separation of skin cells and the entry of pathogens. ExhC is of clinical importance since in addition to causing exfoliation in pigs and mice, it induces necrosis in multiple mammalian cell lines, a property not observed for other ETs. Previous experiments have implicated the ExhC fragment in causing necrosis. Site-directed mutagenesis of specific residues within this fragment were studied and led to the design of an ExhC variant containing four-point mutations (ExhC) lacking necrotic potential but retaining nearly wild-type (wt) levels of enzymatic activity. Moreover, the determination of the ExhC and ExhC crystal structures identified the conformation in the necrosis-linked region. These results constitute an important step toward the understanding of the mechanisms underlying the necrotic and epidermolytic activity of ExhC.

PubMed: 38287568
DOI: 10.1016/j.ijbiomac.2023.127741

Experimental method

X-RAY DIFFRACTION (1.57 Å)