5jiu | pdb_00005jiu
The crystal structure of RanBPM/9 IUS-SPRY domain in complex with DDX-4 peptide
Structural highlights
Function[RANB9_HUMAN] May act as an adapter protein to couple membrane receptors to intracellular signaling pathways. May be involved in signaling of ITGB2/LFA-1 and other integrins. Enhances HGF-MET signaling by recruiting Sos and activating the Ras pathway. Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but not affect estrogen-induced transactivation. Stabilizes TP73 isoform Alpha, probably by inhibiting its ubiquitination, and increases its proapoptotic activity. Inhibits the kinase activity of DYRK1A and DYRK1B. Inhibits FMR1 binding to RNA (By similarity).[1] [2] [3] [4] [5] [6] [7] [DDX4_MOUSE] Probable ATP-dependent RNA helicase required during spermatogenesis to repress transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Involved in the secondary piRNAs metabolic process, the production of piRNAs in fetal male germ cells through a ping-pong amplification cycle.[8] Publication Abstract from PubMedRanBPM and RanBP10 are non-canonical members of the Ran binding protein family that lack the Ran binding domain and do not associate with Ran GTPase in vivo. Rather, they have been shown to be scaffolding proteins that are important for a variety of cellular processes, and both of these proteins contain a SPRY domain, which has been implicated in mediating protein-protein interactions with a variety of targets including the DEAD-box containing ATP-dependent RNA helicase (DDX-4). In this study, we have determined the crystal structures of the SPIa and the ryanodine receptor domain and of approximately 70 upstream residues (immediate upstream to SPRY motif) of both RanBPM and RanBP10. They are almost identical, composed of a beta-sandwich fold with a set of two helices on each side located at the edge of the sheets. A unique shallow binding surface is formed by highly conserved loops on the surface of the beta-sheet with two aspartates on one end, a positive patch on the opposite end, and a tryptophan lining at the bottom of the surface. The 20-mer peptide (residues 228-247) of human DDX-4, an ATP-dependent RNA helicase known to regulate germ cell development, binds to this surface with a KD of ~13muM. The crystal structure of the peptide complex and the mutagenesis studies elucidate how RanBPM can recognize its interaction partners to function in gametogenesis. Structural Basis for the Interaction between the IUS-SPRY Domain of RanBPM and DDX-4 in Germ Cell Development.,Hong SK, Kim KH, Song EJ, Kim EE J Mol Biol. 2016 Oct 23;428(21):4330-4344. doi: 10.1016/j.jmb.2016.09.004. Epub, 2016 Sep 10. PMID:27622290[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||||||
