The BioGRID | PUBLICATION VIEW

	J. Cell Biol. Oct (2007); 179(1):75-86
Two regulatory steps of ER-stress sensor Ire1 involving its cluster formation and interaction with unfolded proteins-
Kimata Y, Ishiwata-Kimata Y, Ito T, Hirata A, Suzuki T, Oikawa D, Takeuchi M, Kohno K
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan- kimata@zero-ad-jp
Abstract: Chaperone protein BiP binds to Ire1 and dissociates in response to endoplasmic reticulum -ER- stress- However, it remains unclear how the signal transducer Ire1 senses ER stress and is subsequently activated- The crystal structure of the core stress-sensing region -CSSR- of yeast Ire1 luminal domain led to the controversial suggestion that the molecule can bind to unfolded proteins- We demonstrate that, upon ER stress, Ire1 clusters and actually interacts with unfolded proteins- Ire1 mutations that affect these phenomena reveal that Ire1 is activated via two steps, both of which are ER stress regulated, albeit in different ways- In the first step, BiP dissociation from Ire1 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-
[PUBMED: 17923530]