| First Author | Koyama M | Year | 2010 |
| Journal | EMBO J | Volume | 29 |
| Issue | 12 | Pages | 2002-13 |
| PubMed ID | 20485264 | Mgi Jnum | J:161313 |
| Mgi Id | MGI:4457980 | Doi | 10.1038/emboj.2010.89 |
| Citation | Koyama M, et al. (2010) An allosteric mechanism to displace nuclear export cargo from CRM1 and RanGTP by RanBP1. EMBO J 29(12):2002-13 |
| abstractText | The karyopherin CRM1 mediates nuclear export of proteins and ribonucleoproteins bearing a leucine-rich nuclear export signal (NES). To elucidate the precise mechanism by which NES-cargos are dissociated from CRM1 in the cytoplasm, which is important for transport directionality, we determined a 2.0-A resolution crystal structure of yeast CRM1:RanBP1:RanGTP complex, an intermediate in the disassembly of the CRM1 nuclear export complex. The structure shows that on association of Ran-binding domain (RanBD) of RanBP1 with CRM1:NES-cargo:RanGTP complex, RanBD and the C-terminal acidic tail of Ran induce a large movement of the intra-HEAT9 loop of CRM1. The loop moves to the CRM1 inner surface immediately behind the NES-binding site and causes conformational rearrangements in HEAT repeats 11 and 12 so that the hydrophobic NES-binding cleft on the CRM1 outer surface closes, squeezing out the NES-cargo. This allosteric mechanism accelerates dissociation of NES by over two orders of magnitude. Structure-based mutagenesis indicated that the HEAT9 loop also functions as an allosteric autoinhibitor to stabilize CRM1 in a conformation that is unable to bind NES-cargo in the absence of RanGTP. |
