2007 Fiscal Year Final Research Report Summary
The mechanism for sensing ER stress by Irel
| Project/Area Number |
18570179
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Nara Institute of Science and Technology |
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Principal Investigator |
KIMATA Yukio Nara Institute of Science and Technology, Graduate School of Biological Sciences, Associate professor (60263448)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Molecular biology / Cell biology / Endoplasmic reticulum / ER stress / Molecular chaperone / Signal transduction / Protein |
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| Research Abstract |
Chaperone protein BiP binds to Irel and dissociate in response to endoplasmic reticulum (ER) stress. However, it remains unclear how the signal transducer Irel sences ER stress and is subsequently activated. The crystal structure of the core stress-sensing region (CSSR) of yeast Irel luminal domain led to the controversial suggestion that the molecule can bind to unfolded proteins. We demonstrate that, upon ER stress, Irel clusters and actually interacts with unfolded proteins. Irel mutations that affect these phenomena reveal that Irel is activated via two steps, both of which are ER stress-regulated, albeit in different ways. In the first step, BiP dissociation from Irel leads to its cluster formation. In the second step, direct interaction of unfolded proteins with the CSSR orients the cytosolic effector domains of clustered Ire1 molecules.
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