5ZTM
Crystal structure of MLE dsRBDs in complex with roX2 (R2H1)
Summary for 5ZTM
| Entry DOI | 10.2210/pdb5ztm/pdb |
| Descriptor | Dosage compensation regulator, non-coding mRNA sequence roX2 (2 entities in total) |
| Functional Keywords | helicase, lncrna, hydrolase-rna complex, hydrolase/rna |
| Biological source | Drosophila melanogaster (Fruit fly) More |
| Total number of polymer chains | 3 |
| Total formula weight | 76354.92 |
| Authors | Lv, M.Q.,Tang, Y.J. (deposition date: 2018-05-04, release date: 2019-03-06, Last modification date: 2023-11-22) |
| Primary citation | Lv, M.,Yao, Y.,Li, F.,Xu, L.,Yang, L.,Gong, Q.,Xu, Y.Z.,Shi, Y.,Fan, Y.J.,Tang, Y. 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. Nucleic Acids Res., 47:3142-3157, 2019 Cited by PubMed Abstract: 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 2.90Å 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. PubMed: 30649456DOI: 10.1093/nar/gky1308 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.899 Å) |
Structure validation
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