Structure of a sigma28-regulated nonflagellar virulence protein from Campylobacter jejuni.
Campylobacter jejuni, a Gram-negative motile bacterium, is a leading cause of human gastrointestinal infections. Although the mechanism of C.jejuni-mediated enteritis appears to be multifactorial, flagella play complex roles in the virulence of this human pathogen. Cj0977 is a recently identified virulence factor in C. jejuni and is expressed by a sigma(28) promoter that controls late genes in the flagellar regulon. A Cj0977 mutant strain is fully motile but significantly reduced in the invasion of intestinal epithelial cells in vitro. Here, we report the crystal structure of the major structural domain of Cj0977, which reveals a homodimeric "hot-dog" fold architecture. Of note, the characteristic hot-dog fold has been found in various coenzyme A (CoA) compound binding proteins with numerous oligomeric states. Structural comparison with other known hot-dog fold proteins locates a putative binding site for an acyl-CoA compound in the Cj0977 protein. Structure-based site-directed mutagenesis followed by invasion assays indicates that key residues in the putative binding site are indeed essential for the Cj0977 virulence function, suggesting a possible function of Cj0977 as an acyl-CoA binding regulatory protein.
Yokoyama
Takeshi
T
Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
Paek
Seonghee
S
Ewing
Cheryl P
CP
Guerry
Patricia
P
Yeo
Hye-Jeong
HJ
D000214:Acyl Coenzyme A / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D016123:Campylobacter jejuni / Q000737:chemistry* / Q000472:pathogenicity*; D018360:Crystallography, X-Ray; D019281:Dimerization; D020895:Enterocytes / Q000382:microbiology; D005407:Flagella / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D016415:Sequence Alignment; D012808:Sigma Factor / Q000378:metabolism*; D040681:Structural Homology, Protein; D037521:Virulence Factors / Q000737:chemistry* / Q000302:isolation & purification
D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; C064971:FliA protein, Bacteria; D021122:Protein Subunits; D012808:Sigma Factor; D037521:Virulence Factors