A03-1：Protein metalation that controls biometal dynamics in the cells
Taiho Kambe
(Graduate School of Biostudies, Kyoto University)
Lab website
More than 10% of the human proteome shows the motif for zinc-binding. Therefore, metalation with zinc within proteins needs to be strictly controlled, and the cells should be equipped with molecular machines to properly supply zinc to the target proteins and enzymes. However, molecular mechanism underlying this process has been largely unknown. Moreover, the metalation process should be closely associated with protein dysfunctions, if it is hijacked by other biometals and toxic metals, which manifests the toxicity. The goal of this project is to elucidate how metalation process is regulated in the cells at a molecular level by focusing on metalation process of zinc mediated by zinc transporters, and extend the evidence for precise understanding how toxic metals impair cellular biometal homeostasis, such as zinc, through metalation process.
Major publications
T. Takeda, S. Miyazaki, M. Kobayashi, K. Nishino, T. Goto, M. Matsunaga, M. Ooi, H. Shirakawa, F. Tani, T. Kawamura, M. Komai, and *T. Kambe
“Zinc deficiency causes delayed ATP clearance and adenosine generation in rats and cell culture models”
Communications Biology, 2018, 1, 113
doi: 10.1038/s42003-018-0118-3
Press release
Y. Nishito, N. Tsuji, H. Fujishiro, T. Takeda, T. Yamazaki, F. Teranishi, F. Okazaki, A. Matsunaga, K. Tuschl, R. Rao, S. Kono, H. Miyajima, H. Narita, S. Himeno, and *T. Kambe
“Direct Comparison of Manganese Detoxification/Efflux Proteins and Molecular Characterization of ZnT10 Protein as a Manganese Transporter”
The Journal of Biological Chemistry, 2016, 291, 14773–14787
doi: 10.1074/jbc.M116.728014
N. Itsumura, Y. Kibihara, K. Fukue, A. Miyata, K. Fukushima, R. Tamagawa-Mineoka, N. Katoh, Y. Nishito, R. Ishida, H. Narita, H. Kodama, and *T. Kambe
“Novel mutations in SLC30A2 involved in the pathogenesis of transient neonatal zinc deficiency”
Pediatric Research, 2016, 80, 586-594
doi: 10.1038/pr.2016.108
Press release
A. Fukunaka, Y. Kurokawa, F. Teranishi, I. Sekler, K. Oda, M. L. Ackland, V. Faundez, M. Hiromura, S. Masuda, M. Nagao, S. Enomoto, and *T. Kambe
“Tissue non-specific alkaline phosphatase is activated via a two-step mechanism by zinc transport complexes in the early secretory pathway”
The Journal of Biological Chemistry, 2011, 286, 16363–16373
doi: 10.1074/jbc.M111.227173
T. Kambe and *G. K. Andrews
“Novel proteolytic processing of the ectodomain of the zinc transporter ZIP4 (Slc39a4) during zinc deficiency is inhibited by acrodermatitis enteropathica mutations”
Molecular and Cellular Biology, 2009, 29, 129–139
doi: 10.1128/MCB.00963-08