|Title||Structure and mechanism of the uracil transporter UraA.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Lu, F, Li, S, Jiang, Y, Jiang, J, Fan, H, Lu, G, Deng, D, Dang, S, Zhang, X, Wang, J, Yan, N|
|Date Published||2011 Apr 14|
|Keywords||Biological Transport, Crystallography, X-Ray, Escherichia coli, Escherichia coli Proteins, Hydrogen Bonding, Membrane Transport Proteins, Models, Biological, Models, Molecular, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Protons, Structure-Activity Relationship, Uracil|
The nucleobase/ascorbate transporter (NAT) proteins, also known as nucleobase/cation symporter 2 (NCS2) proteins, are responsible for the uptake of nucleobases in all kingdoms of life and for the transport of vitamin C in mammals. Despite functional characterization of the NAT family members in bacteria, fungi and mammals, detailed structural information remains unavailable. Here we report the crystal structure of a representative NAT protein, the Escherichia coli uracil/H(+) symporter UraA, in complex with uracil at a resolution of 2.8 Å. UraA has a novel structural fold, with 14 transmembrane segments (TMs) divided into two inverted repeats. A pair of antiparallel β-strands is located between TM3 and TM10 and has an important role in structural organization and substrate recognition. The structure is spatially arranged into a core domain and a gate domain. Uracil, located at the interface between the two domains, is coordinated mainly by residues from the core domain. Structural analysis suggests that alternating access of the substrate may be achieved through conformational changes of the gate domain.