5ztm | pdb_00005ztm

Crystal structure of MLE dsRBDs in complex with roX2 (R2H1)

spinqualitylabelsall models 5ztm, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ztm is a 3 chain structure with sequence from Drome and Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: GTP Gene: mle, nap, CG11680 (DROME) Activity: RNA helicase, with EC number 3.6.4.13 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MLE_DROME] Required in males for dosage compensation of X chromosome linked genes. Mle, msl-1 and msl-3 are colocalized on X chromosome. Each of the msl proteins requires all the other msls for wild-type X-chromosome binding. Probably unwinds double-stranded DNA and RNA in a 3' to 5' direction. Publication Abstract from PubMed In Drosophila, dosage compensation globally upregulates the expression of genes located on male single X-chromosome. Maleless (MLE) helicase plays an essential role to incorporate the roX lncRNA into the dosage compensation complex (MSL-DCC), and such function is essentially dependent on its dsRNA-binding domains (dsRBDs). Here, we report a 2.90A crystal structure of tandem dsRBDs of MLE in complex with a 55mer stem-loop of roX2 (R2H1). MLE dsRBDs bind to R2H1 cooperatively and interact with two successive minor grooves and a major groove of R2H1, respectively. The recognition of R2H1 by MLE dsRBDs involves both shape- and sequence-specificity. Moreover, dsRBD2 displays a stronger RNA affinity than dsRBD1, and mutations of key residues in either MLE dsRBD remarkably reduce their affinities for roX2 both in vitro and in vivo. In Drosophila, the structure-based mle mutations generated using the CRISPR/Cas9 system, are partially male-lethal and indicate the inter-regulation among the components of the MSL-DCC at multiple levels. Hence, our research provides structural insights into the interactions between MLE dsRBDs and R2H1 and facilitates a deeper understanding of the mechanism by which MLE tandem dsRBDs play an indispensable role in specific recognition of roX and the assembly of the MSL-DCC in Drosophila dosage compensation. Structural insights reveal the specific recognition of roX RNA by the dsRNA-binding domains of the RNA helicase MLE and its indispensable role in dosage compensation in Drosophila.,Lv M, Yao Y, Li F, Xu L, Yang L, Gong Q, Xu YZ, Shi Y, Fan YJ, Tang Y Nucleic Acids Res. 2019 Jan 15. pii: 5289492. doi: 10.1093/nar/gky1308. PMID:30649456 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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