title: The structural basis of modularity in ECF-type ABC transporters.
abstract: Energy coupling factor (ECF) transporters are used for the uptake of vitamins in Prokarya. They consist of an integral membrane protein that confers substrate specificity (the S-component) and an energizing module that is related to ATP-binding cassette (ABC) transporters. S-components for different substrates often do not share detectable sequence similarity but interact with the same energizing module. Here we present the crystal structure of the thiamine-specific S-component ThiT from Lactococcus lactis at 2.0 Å. Extensive protein-substrate interactions explain its high binding affinity for thiamine (K(d) ~10(-10) M). ThiT has a fold similar to that of the riboflavin-specific S-component RibU, with which it shares only 14% sequence identity. Two alanines in a conserved motif (AxxxA) located on the membrane-embedded surface of the S-components mediate the interaction with the energizing module. Based on these findings, we propose a general transport mechanism for ECF transporters.
authors.affiliation: University of Groningen, Groningen Biomolecular Science and Biotechnology Institute, Groningen, The Netherlands.
authors.forename: Guus B
authors.initials: GB
authors.lastname: Erkens
authors.forename: Ronnie P-A
authors.initials: RP
authors.lastname: Berntsson
authors.forename: Faizah
authors.initials: F
authors.lastname: Fulyani
authors.forename: Maria
authors.initials: M
authors.lastname: Majsnerowska
authors.forename: Andreja
authors.initials: A
authors.lastname: Vujičić-Žagar
authors.forename: Josy
authors.initials: J
authors.lastname: Ter Beek
authors.forename: Bert
authors.initials: B
authors.lastname: Poolman
authors.forename: Dirk Jan
authors.initials: DJ
authors.lastname: Slotboom
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry*; D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D013294:Lactococcus lactis / Q000378:metabolism*; D008958:Models, Molecular; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D013831:Thiamine / Q000737:chemistry / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D000255:Adenosine Triphosphate; D013831:Thiamine