2011 Fiscal Year Final Research Report
The elucidation of the zinc supplying mechanism of zinc requiring enzyme by zinc transporters
| Project/Area Number |
22890237
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
FUKUNAKA Ayako 独立行政法人理化学研究所, 複数分子イメージング研究チーム, 研究員 (60586402)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 亜鉛トランスポーター / 亜鉛要求性酵素 / 分泌経路 / 活性化機構 |
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| Research Abstract |
The reduced activity of TNAP in DT40 cells deficient of two ZnT complexes(ZnT5/ZnT6 heterodimer and ZnT7 homo-oligomer) was not restored by zinc supplementation nor by exogenous expression of other ZnTs that increase the zinc content in the early secretory pathway. Moreover the expression of ZnT5/ZnT6 heterodimers reconstituted with zinc-transport-incompetent ZnT5 mutant failed to restore TNAP activity, but could stabilize the TNAP protein as the apo-form. These findings demonstrate that TNAP is activated not simply by passive zinc binding, but by an elaborate two-step mechanism via protein stabilization followed by enzyme conversion from the apo-to the holo-form with zinc loaded by ZnT complexes in the early secretory pathway.
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[Journal Article] Tissue non-specific alkaline phosphatase is activated via a two-step mechanism by zinc transporter complexes in the early secretory pathway2011
Author(s)
Fukunaka A, Kurokawa Y, Teranishi F, Sekler I, Oda K, Ackland M. L, Faundez V, Hiromura M, Masuda S, Nagao M, Enomoto S, Kambe T
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Journal Title
J Biol. Chem
Volume: 286
Pages: 16363-16373
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