Structural Biology

Biography

Biography: Mi Sun Jin

Abstract

The sodium-dependent citrate transporter of Klebsiella pneumoniae (KpCitS) belongs to the 2-hydroxycarboxylate transporter (2-HCT) family and allows the cell to use citrate as sole carbon and energy source in anaerobic conditions. We present crystal structures of KpCitS in its citrate-bound outward-facing as well as citrate-free inward-facing state. The structure of the asymmetric KpCitS homodimer containing both outward- and inward-open protomers was also determined. The structures reveal that the KpCitS dimerization domain remains stationary throughout the transport cycle due to an extensive hydrogen bond network as well as hydrophobic interactions. In contrast, its transport domain undergoes a ~35° rigid-body rotation and a ~17 Å translocation perpendicular to the membrane to expose the substrate-binding site alternately to either side of the membrane. Homology models of two other 2-HCT proteins based on the KpCitS structure offer structural insights into their differences in substrate specificity at a molecular level. On the basis of our results and previous biochemical data, we propose that the activity of the 2-HCT family of transporters involves an elevator-like movement in which the transport domain itself traverses the lipid bilayer, carrying the substrate into the cell in a sodium-dependent manner.

References:

1. Kim JH, Song DH, Youn SJ, Kim JW, Cho G, Kim SC, Lee H, Jin MS, Lee JO (2016) Crystal structures of mono- and bi-specific diabodies and reduction of their structural flexibility by introduction of disulfide bridges at the Fv interface. Scientific reports, 6, 34515.
2. Mi Sun Jin, Michael L. Oldham, Qiuju Zhang, Jue Chen (2012) Crystal structure of the multidrug transporter P-glycoprotein from C. elegans. Nature, 490, 566-9.
3. Jin Young Kang, Xuehua Nan, Mi Sun Jin, Suk-Jun Youn, Young Hee Ryu, Shinji Ma, Seung Hyun Han, Sang-Gi Paik, Hayyoung Lee, Jie-Oh Lee (2009) Recognition of lipopeptide patterns by TLR2-TLR6 heterodimer. Immunity, 31, 873-84.
4. Mi Sun Jin, Jie-Oh Lee (2008) Structures of the Toll-like Receptor Family and Its Ligand Complexes. Immunity, 29, 182-91.
5. Mi Sun Jin, Sung Eun Kim, Jin Young Heo, Mi Eun Lee, Ho Min Kim, Sang-Gi Paik, Hayyoung Lee, Jie-Oh Lee (2007) Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a triacylated lipopeptide. Cell, 130, 1071-82.