5Z7Q

Crystal structure of Bacillus cereus flagellin

Summary for 5Z7Q

• Entry DOI: 10.2210/pdb5z7q/pdb
• Descriptor: Flagellin (2 entities in total)
• Functional Keywords: bacteria, flagellin, adjuvant, immune system
• Biological source: Bacillus cereus (strain ATCC 14579 / DSM 31 / JCM 2152 / NBRC 15305 / NCIMB 9373 / NRRL B-3711)
• Cellular location: Secreted : Q81FD4
• Total number of polymer chains: 1
• Total formula weight: 18774.64

Authors

Kim, M.,Hong, M. (deposition date: 2018-01-30, release date: 2018-05-30, Last modification date: 2023-11-22)

Primary citation

Il Kim, M.,Lee, C.,Park, J.,Jeon, B.Y.,Hong, M.
Crystal structure of Bacillus cereus flagellin and structure-guided fusion-protein designs
Sci Rep, 8:5814-5814, 2018

PubMed Abstract: Flagellin is a major component of the flagellar filament. Flagellin also functions as a specific ligand that stimulates innate immunity through direct interaction with Toll-like receptor 5 (TLR5) in the host. Because flagellin activates the immune response, it has been of interest to develop as a vaccine adjuvant in subunit vaccines or antigen fusion vaccines. Despite the widespread application of flagellin fusion in preventing infectious diseases, flagellin-antigen fusion designs have never been biophysically and structurally characterized. Moreover, flagellin from Salmonella species has been used extensively despite containing hypervariable regions not required for TLR5 that can cause an unexpected immune response. In this study, flagellin from Bacillus cereus (BcFlg) was identified as the smallest flagellin molecule containing only the conserved TLR5-activating D0 and D1 domains. The crystal structure of BcFlg was determined to provide a scheme for fusion designs. Through homology-based modeling and comparative structural analyses, diverse fusion strategies were proposed. Moreover, cellular and biophysical analysis of an array of fusion constructs indicated that insertion fusion at BcFlg residues 178-180 does not interfere with the protein stability or TLR5-stimulating capacity of flagellin, suggesting its usefulness in the development and optimization of flagellin fusion vaccines.

PubMed: 29643437
DOI: 10.1038/s41598-018-24254-w

Experimental method

X-RAY DIFFRACTION (1.85 Å)