title: An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni inferred from the structure of an extracytoplasmic solute receptor protein.
abstract: Campylobacter jejuni is a Gram-negative food-borne pathogen associated with gastroenteritis in humans as well as cases of the autoimmune disease Guillain-Barré syndrome. C. jejuni is asaccharolytic because it lacks an active glycolytic pathway for the use of sugars as a carbon source. This suggests an increased reliance on amino acids as nutrients and indeed the genome sequence of this organism indicates the presence of a number of amino acid uptake systems. Cj0982, also known as CjaA, is a putative extracytoplasmic solute receptor for one such uptake system as well as a major surface antigen and vaccine candidate. The crystal structure of Cj0982 reveals a two-domain protein with density in the enclosed cavity between the domains that clearly defines the presence of a bound cysteine ligand. Fluorescence titration experiments were used to demonstrate that Cj0982 binds cysteine tightly and specifically with a K(d) of approximately 10(-7) M consistent with a role as a receptor for a high-affinity transporter. These data imply that Cj0982 is the binding protein component of an ABC-type cysteine transporter system and that cysteine uptake is important in the physiology of C. jejuni.
authors.affiliation: Structural Biology Laboratory, Department of Chemistry, University of York, York, YO10 5YW, UK.
authors.forename: Axel
authors.initials: A
authors.lastname: Müller
authors.forename: Gavin H
authors.initials: GH
authors.lastname: Thomas
authors.forename: Richard
authors.initials: R
authors.lastname: Horler
authors.forename: James A
authors.initials: JA
authors.lastname: Brannigan
authors.forename: Elena
authors.initials: E
authors.lastname: Blagova
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Levdikov
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Fogg
authors.forename: Keith S
authors.initials: KS
authors.lastname: Wilson
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Wilkinson
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D000595:Amino Acid Sequence; D026921:Amino Acid Transport Systems, Neutral / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D016123:Campylobacter jejuni / Q000737:chemistry*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013050:Spectrometry, Fluorescence; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D026921:Amino Acid Transport Systems, Neutral; D001426:Bacterial Proteins; D002352:Carrier Proteins; C503090:CjaA protein, Campylobacter jejuni; D014443:Tyrosine; D003545:Cysteine