2012 Fiscal Year Final Research Report
Nuclear export mediated by CRM1: from X-ray structures to mechanism in living cells
| Project/Area Number |
23770110
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Structural biochemistry
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2011 – 2012
|
| Keywords | 構造生物学 |
|---|
| Research Abstract |
Nucleocytoplasmic transport of macromolecues is a fundamental activity essential for a plethora of physiological functions of eukaryotic cells. CRM1 is a major nuclear export receptor (exportin) that mediates nuclear export of cargo macromolecules bearing a leucine-rich nuclear export signal (NES). In the nucleus, CRM1 binds cooperatively to RanGTP and NES-cargo, forming a trimeric complex. In this study, we determined X-ray crystal structure of unliganded Saccharomyces cerevisiaeCRM1 at 2.1-Åresolution. Comparison with the structure of CRM1-NES-RanGTP complex and structure-based mutational analyses revealed the mechanism of autoinhibition of CRM1 and the mechanism by which the binding of NES to CRM1 depends on RanGTP.
|
