2020同步年報

046 ACTIVITY REPORT 2020 Fig. 3 : Variants in h PiT2 linked to brain calcification disease were mapped onto the modeled h PiT2 structure. Variants are shown as spheres and grouped into five categories: Pi-binding (orange), Na-binding (green), N-PD001131 (pink), C-PD001131 (blue) and dimer (yel- low). The Hs/Tm number is also labelled. The Pi and Na binding sites are indicated with dashed outlines. [Reproduced from Ref. 2] clinical data from variants in h PiT. For example, the variant residues in hPiT are all found at essential positions or are involved in sodium and phosphate binding; some are near the inner membrane and might regulate Pi transport; a few are in the dimerization domain; others are located in the extracellular soluble (S) domain. These findings highlight how the Tm PiT structural data might inform the molecular mechanisms underlying human diseases associated with mutations in h PiT. In summary, the Tm PiT-Pi/Na complex contains a phos- phate and three sodium ions tightly bound with TM1/6 and HP1/HP2. Structural differences occur between subunits A and B near the inner gate, in loops L7/LHP2 and TM8. These findings provide a structural basis for disease-causing muta- tions in h PiT. Tm PiT is the first complete structural study of a sodium-dependent phosphate transporter. The resolved three-dimensional structure of Tm PiT might help establish therapeutic targets for PiT dysfunction diseases. (Reported by Jia-Yin Tsai, National Tsing Hua University) This report features the work of Yuh-Ju Sun and her collabo- rators published in Sci. Adv. 6 , eabb4024 (2020). TPS 05A Protein Microcrystallography • Protein Crystallography • Biological Macromolecules, Protein Structures, Life Sci- ence References 1. I. C. Forster, N. Hernando, J. Biber, H. Murer, Mol. Aspects Med. 34 , 386 (2013). 2. J.-Y. Tsai, C.-H. Chu, M.-G. Lin, Y.-H. Chou, R.-Y. Hung, C.-D. Hsiao, Y.-J. Sun, Sci. Adv. 6 , eabb4024 (2020). 3. R. R. Lemos, E. M. Ramos, A. Legati, G. Nicolas, E. M. Jenkinson, J. H. Livingston, Y. J. Crow, D. Campion, G. Coppola, J. R. Oliveira, Hum. Mutat. 36 , 489 (2015).