title: Structure of CfaA suggests a new family of chaperones essential for assembly of class 5 fimbriae.
abstract: Adhesive pili on the surface of pathogenic bacteria comprise polymerized pilin subunits and are essential for initiation of infections. Pili assembled by the chaperone-usher pathway (CUP) require periplasmic chaperones that assist subunit folding, maintain their stability, and escort them to the site of bioassembly. Until now, CUP chaperones have been classified into two families, FGS and FGL, based on the short and long length of the subunit-interacting loops between its F1 and G1 β-strands, respectively. CfaA is the chaperone for assembly of colonization factor antigen I (CFA/I) pili of enterotoxigenic E. coli (ETEC), a cause of diarrhea in travelers and young children. Here, the crystal structure of CfaA along with sequence analyses reveals some unique structural and functional features, leading us to propose a separate family for CfaA and closely related chaperones. Phenotypic changes resulting from mutations in regions unique to this chaperone family provide insight into their function, consistent with involvement of these regions in interactions with cognate subunits and usher proteins during pilus assembly.
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Rui
authors.initials: R
authors.lastname: Bao
authors.affiliation: Enteric Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, Maryland, United States of America.
authors.forename: April
authors.initials: A
authors.lastname: Fordyce
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
authors.forename: Yu-Xing
authors.initials: YX
authors.lastname: Chen
authors.affiliation: Enteric Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, Maryland, United States of America.
authors.forename: Annette
authors.initials: A
authors.lastname: McVeigh
authors.affiliation: Enteric Diseases Department, Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, Maryland, United States of America; Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Savarino
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Di
authors.initials: D
authors.lastname: Xia
mesh_terms: D054307:Enterotoxigenic Escherichia coli / Q000378:metabolism / Q000472:pathogenicity* / Q000648:ultrastructure*; D004927:Escherichia coli Infections / Q000378:metabolism; D036781:Fimbriae Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D010861:Fimbriae, Bacterial / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation
chemical_list: D018832:Molecular Chaperones; D036781:Fimbriae Proteins