5ecj

Crystal structure of monobody Mb(S4) bound to Prdm14 in complex with Mtgr1

spinqualitylabelsall models 5ecj, resolution 3.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ecj is a 4 chain structure with sequence from Human and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: Cbfa2t2, Cbfa2t2h, Mtgr1 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PRD14_MOUSE] Transcription factor that has both positive and negative roles on transcription. Plays a role in cellular pluripotency (By similarity). Essential for germ cell development at 2 levels: the reacquisition of potential pluripotency, including SOX2 up-regulation, and successful epigenetic reprogramming, characterized by EHMT1 repression. Publication Abstract from PubMed Prdm14 is a sequence-specific transcriptional regulator of embryonic stem cell (ESC) pluripotency and primordial germ cell (PGC) formation. It exerts its function, at least in part, through repressing genes associated with epigenetic modification and cell differentiation. Here, we show that this repressive function is mediated through an ETO-family co-repressor Mtgr1, which tightly binds to the pre-SET/SET domains of Prdm14 and co-occupies its genomic targets in mouse ESCs. We generated two monobodies, synthetic binding proteins, targeting the Prdm14 SET domain and demonstrate their utility, respectively, in facilitating crystallization and structure determination of the Prdm14-Mtgr1 complex, or as genetically encoded inhibitor of the Prdm14-Mtgr1 interaction. Structure-guided point mutants and the monobody abrogated the Prdm14-Mtgr1 association and disrupted Prdm14's function in mESC gene expression and PGC formation in vitro. Altogether, our work uncovers the molecular mechanism underlying Prdm14-mediated repression and provides renewable reagents for studying and controlling Prdm14 functions. ETO family protein Mtgr1 mediates Prdm14 functions in stem cell maintenance and primordial germ cell formation.,Nady N, Gupta A, Ma Z, Swigut T, Koide A, Koide S, Wysocka J Elife. 2015 Nov 2;4. pii: e10150. doi: 10.7554/eLife.10150. PMID:26523391 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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