3w3y

Crystal structure of Kap121p bound to Nup53p

spinqualitylabelsall models 3w3y, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3w3y is a 2 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 3w3t, 3w3u, 3w3v, 3w3w, 3w3x, 3w3z Gene: PSE1, KAP121, YMR308C, YM9952.10C (Baker's yeast), NUP53, YMR153W, YM8520.02 (Baker's yeast) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [IMB3_YEAST] Involved in the nuclear import of ribosomal proteins. Binds to nucleoporins and the GTP-bound form of GSP1 (Ran). Plays a role in protein secretion. [NUP53_YEAST] Functions as a component of the nuclear pore complex (NPC). NPC components, collectively referred to as nucleoporins (NUPs), can play the role of both NPC structural components and of docking or interaction partners for transiently associated nuclear transport factors. Active directional transport is assured by both, a Phe-Gly (FG) repeat affinity gradient for these transport factors across the NPC and a transport cofactor concentration gradient across the nuclear envelope (GSP1 and GSP2 GTPases associated predominantly with GTP in the nucleus, with GDP in the cytoplasm). NUP53 may play an important role in cell cycle regulation by inhibiting PSE1 transport functions during mitosis and sequestration of MAD1-MAD2 in a cell cycle-dependent manner. It also seems to play an important role in de novo NPC assembly by associating with nuclear membranes and driving their proliferation. Publication Abstract from PubMed Kap121p (also known as Pse1p) is an essential karyopherin that mediates nuclear import of a plethora of cargoes including cell-cycle regulators, transcription factors, and ribosomal proteins in Saccharomyces cerevisiae. It has been proposed that the spindle assembly checkpoint signaling triggers molecular rearrangements of nuclear pore complexes and thereby arrests Kap121p-mediated nuclear import at metaphase, while leaving import mediated by other karyopherins unaffected. The Kap121p-specific import inhibition is required for normal progression through mitosis. To understand the structural basis for Kap121p-mediated nuclear import and its unique regulatory mechanism during mitosis, we determined crystal structures of Kap121p in isolation and also in complex with either its import cargoes or nucleoporin Nup53p or RanGTP. Kap121p has a superhelical structure composed of 24 HEAT repeats. The structures of Kap121p-cargo complexes define a non-conventional nuclear localization signal (NLS) that has a consensus sequence of KV/IxKx1-2K/H/R. The structure of Kap121p-Nup53p complex shows that cargo and Nup53p compete for the same high-affinity binding site, explaining how Nup53p binding forces cargo release when the Kap121p binding site of Nup53p is exposed during mitosis. Comparison of the NLS- and RanGTP-complexes reveals that RanGTP binding not only occludes the cargo-binding site but also forces Kap121p into a conformation that is incompatible with NLS recognition. Structural basis for cell-cycle dependent nuclear import mediated by the karyopherin Kap121p.,Kobayashi J, Matsuura Y J Mol Biol. 2013 Mar 27. pii: S0022-2836(13)00194-0. doi:, 10.1016/j.jmb.2013.02.035. PMID:23541588 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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