Sandbox Reserved 485
From Proteopedia
This Sandbox is Reserved from 13/03/2012, through 01/06/2012 for use in the course "Proteins and Molecular Mechanisms" taught by Robert B. Rose at the North Carolina State University, Raleigh, NC USA. This reservation includes Sandbox Reserved 451 through Sandbox Reserved 500. |
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RanBP does not influence the rate-limiting step of the reaction (cleavage of GTP/ loss of P(i), but does influence the dynamics of the Ran-RanGAP interactions, allowing a 20-fold stimulation of an association reaction Mechanism of Action The Ran cycle plays a major function in translocating cargo such as RNA and proteins from and to the cytoplasm and nucleus. Cargo that is imported are typically proteins that are synthesized in the cytoplasm but function in the nucleus. A receptor protein known as an importin recognizes and binds to the nuclear localization signal, NLS, located on the cytoplasmic cargo. Importin-NLS protein complex is then able to be transported from the cytoplasm through the nuclear pore complex into the nucleus. Once inside the nucleus, the importin binds to Ran-GTP, allowing the release of the protein from the importin. The Ran-GTP-importin complex migrates back through the nuclear pore complex to release the importin back into the cytosplasm for reuse as Ran-GTP is hydrolyzed to Ran-GDP. The export of cargo into the cytoplasm typically involves RNA molecules that are synthesized in the nucleus but function in the cytoplasm. The receptor protein known as exportin binds to Ran-GTP within the nucleus to promote the recognition and binding of exportin to the nuclear export signals, NES, the is located on the RNA bound cargo protein. The exportin then mediates the transport of the complex through the nuclear pores The key to the import and export of cargo material is dependent on the concentration of Ran-GTP. The concentration of Ran-GTP is maintained by guanine-nucleotide exchange factor, GEF, in the nucleus and a GTPase activating protein, GAP, in the cytosol. Cellular signals indicate the course of the Ran cycle and is especially significant while entering mitosis. Possible Applications Ran also serves a variety of other functions such as mediating DNA synthesis and advancements through a cell cycle. Ran regulates these functions by directing the formation and organization of the microtubule complex. Ran-GTP promotes spindle assembly and the spindle fiber’s attachment to the chromosome. Ran is also involved in activating T cells and the reassembly of the nuclear envelope during mitosis. It is obvious the importance Ran plays within the cell cycle. Defective Ran protein results in irregular reformation of the nuclear envelope, chromosome assembly and microtubule formation. Within the nucleus, malfunctions pertaining to factors associated with specific functions such as splicing and DNA replication These misregulations can result in immunodeficient disorders or X-linked mental retardation. Further research is being conducted to fully understand Ran’s mechanism and regulatory measures.
Resources http://www.ncbi.nlm.nih.gov/pubmed/10078529 http://www.ncbi.nlm.nih.gov/gene/5901 http://www.rcsb.org/pdb/explore/explore.do?structureId=2Y8F http://jcs.biologists.org/content/118/5/843.long http://www.nature.com/scitable/topicpage/coordination-of-cell-cycle-events-by-ran-14428259 |