3wyg
From Proteopedia
Crystal structure of Xpo1p-PKI-Gsp1p-GTP complex
Structural highlights
FunctionGSP1_YEAST GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Essential for cell viability. By analogy with Ras, Ran may be activated when GTP is exchanged for bound GDP by RCC1 and inactivated when GTP is hydrolyzed by Ran upon activation by RanGAP1. Publication Abstract from PubMedProteins and ribonucleoproteins containing a nuclear export signal (NES) assemble with the exportin Xpo1p (yeast CRM1) and Gsp1p-GTP (yeast Ran-GTP) in the nucleus and exit through the nuclear pore complex. In the cytoplasm, Yrb1p (yeast RanBP1) displaces NES from Xpo1p. Efficient export of NES-cargoes requires Yrb2p (yeast RanBP3), a primarily nuclear protein containing nucleoporin-like phenylalanine-glycine (FG) repeats and a low-affinity Gsp1p-binding domain (RanBD). Here, we show that Yrb2p strikingly accelerates the association of Gsp1p-GTP and NES to Xpo1p. We have solved the crystal structure of the Xpo1p-Yrb2p-Gsp1p-GTP complex, a key assembly intermediate that can bind cargo rapidly. Although the NES-binding cleft of Xpo1p is closed in this intermediate, our data suggest that preloading of Gsp1p-GTP onto Xpo1p by Yrb2p, conformational flexibility of Xpo1p, and the low affinity of RanBD enable active displacement of Yrb2p RanBD by NES to occur effectively. The structure also reveals the major binding sites for FG repeats on Xpo1p. Structural insights into how yrb2p accelerates the assembly of the xpo1p nuclear export complex.,Koyama M, Shirai N, Matsuura Y Cell Rep. 2014 Nov 6;9(3):983-95. doi: 10.1016/j.celrep.2014.09.052. Epub 2014, Oct 30. PMID:25437554[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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