6cit

Crystal Structure of MVM NS2 NES Peptide in complex with CRM1-Ran-RanBP1

spinqualitylabelsall models 6cit, resolution 2.03Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6cit is a 4 chain structure with sequence from Homo sapiens, Minute virus of mice and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.027Å Ligands: CL, GNP, GOL, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RAN_HUMAN GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle (By similarity). The complex with BIRC5/ survivin plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. Acts as a negative regulator of the kinase activity of VRK1 and VRK2. Enhances AR-mediated transactivation. Transactivation decreases as the poly-Gln length within AR increases. Publication Abstract from PubMed CRM1 (Exportin1/XPO1) exports hundreds of broadly functioning protein cargos out of the cell nucleus by binding to their classical nuclear export signals (NESs). The 8-15 amino acids long NESs contain 4-5 hydrophobic residues and are highly diverse in both sequence and CRM1-bound structure. Here, we examine the relationship between nuclear export activities of 24 different NES peptides in cells, and their CRM1-NES affinities. We found that binding affinity and nuclear export activity are linearly correlated for NESs with dissociation constants (KDs) between tens of nanomolar to tens of micromolar. NESs with KDs outside this range have significantly reduced nuclear export activities. These include two unusually tight-binding peptides, one from the nonstructural protein 2 of murine minute virus (MVM NS2) and the other a mutant of the Protein Kinase A Inhibitor (PKI) NES. The crystal structure of CRM1-bound MVM NS2(NES) suggests that extraordinarily tight CRM1 binding arises from intramolecular contacts within the NES that likely stabilizes the CRM1-bound conformation in free peptides. This mechanistic understanding led to the design of two novel peptide inhibitors that bind CRM1 with picomolar affinity. Correlation of CRM1-NES affinity with nuclear export activity.,Fu SC, Fung HYJ, Cagatay T, Baumhardt J, Chook YM Mol Biol Cell. 2018 Jun 21:mbcE18020096. doi: 10.1091/mbc.E18-02-0096. PMID:29927350 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Exportin 3D structures GTP-binding protein 3D structures

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