Crystal structure of c5321 : a protective antigen present in uropathogenic Escherichia coli strains displaying an SLR fold
| Autor: | Laura Serino, Ainars Leonchiks, Dunja Urosev, Ilaria Pastorello, David Reverter, Dmitrijs Zhulenkovs, Elena Cartocci, Mario Ferrer-Navarro, Jean-Didier Maréchal, Lionel Costenaro, Xavier Daura, Marco Soriani |
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| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular C5321 Protein Folding Protein Conformation Escherichia coli Vaccines Sel1-like repeat Locus (genetics) Biology medicine.disease_cause Crystallography X-Ray Protein Structure Secondary Microbiology Antigens CD1 Mice Super-helical fold Antibiotic resistance Antigen Structural Biology Consensus Sequence medicine Consensus sequence Animals Uropathogenic Escherichia coli Magnesium Amino Acid Sequence Escherichia coli Antigens Bacterial Binding Sites Helicobacter pylori Protein Stability Escherichia coli Proteins Crystal structure Reverse vaccinology c5321 Protein Structure Tertiary Epitope mapping Structural Homology Protein Epitope Mapping Research Article |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname 'BMC Structural Biology ', vol: 13, pages: 19-1-19-14 (2013) BMC Structural Biology Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| ISSN: | 1472-6807 |
| Popis: | Background Increasing rates of antimicrobial resistance among uropathogens led, among other efforts, to the application of subtractive reverse vaccinology for the identification of antigens present in extraintestinal pathogenic E. coli (ExPEC) strains but absent or variable in non-pathogenic strains, in a quest for a broadly protective Escherichia coli vaccine. The protein coded by locus c5321 from CFT073 E. coli was identified as one of nine potential vaccine candidates against ExPEC and was able to confer protection with an efficacy of 33% in a mouse model of sepsis. c5321 (known also as EsiB) lacks functional annotation and structurally belongs to the Sel1-like repeat (SLR) family. Herein, as part of the general characterization of this potential antigen, we have focused on its structural properties. Results We report the 1.74 Å-resolution crystal structure of c5321 from CFT073 E. coli determined by Se-Met SAD phasing. The structure is composed of 11 SLR units in a topological organisation that highly resembles that found in HcpC from Helicobacter pylori, with the main difference residing in how the super-helical fold is stabilised. The stabilising effect of disulfide bridges in HcpC is replaced in c5321 by a strengthening of the inter-repeat hydrophobic core. A metal-ion binding site, uncharacteristic of SLR proteins, is detected between SLR units 3 and 4 in the region of the inter-repeat hydrophobic core. Crystal contacts are observed between the C-terminal tail of one molecule and the C-terminal amphipathic groove of a neighbouring one, resembling interactions between ligand and proteins containing tetratricopeptide-like repeats. Conclusions The structure of antigen c5321 presents a mode of stabilization of the SLR fold different from that observed in close homologs of known structure. The location of the metal-ion binding site and the observed crystal contacts suggest a potential role in regulation of conformational flexibility and interaction with yet unidentified target proteins, respectively. These findings open new perspectives in both antigen design and for the identification of a functional role for this protective antigen. |
| Databáze: | OpenAIRE |
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