1sxl
From Proteopedia
RESONANCE ASSIGNMENTS AND SOLUTION STRUCTURE OF THE SECOND RNA-BINDING DOMAIN OF SEX-LETHAL DETERMINED BY MULTIDIMENSIONAL HETERONUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
Structural highlights
Function[SXL_DROME] Sex determination switch protein which controls sexual development by sex-specific splicing. Regulates dosage compensation in females by suppressing hyperactivation of X-linked genes. Expression of the embryo-specific isoform is under the control of primary sex-determining signal, which depends on the ratio of X chromosomes relative to autosomes (X:A ratio). Expression occurs in 2X:2A cells, but not in X:2A cells. The X:A ratio seems to be signaled by the relative concentration of the X-linked transcription factors SIS-A and SIS-B. As a result, the embryo-specific product is expressed early only in female embryos and specifies female-adult specific splicing; in the male where it is not expressed, the default splicing gives rise to a truncated non-functional protein. The female-specific isoform specifies the splicing of its own transcript, thereby initiating a positive autoregulatory feedback loop leading to female development pathway. The female-specific isoform controls the sex-specific splicing of transformer (TRA); acts as a translational repressor for male-specific lethal-2 (MSL-2) and prevents male-less (MLE), MSL-1 and MSL-3 proteins from associating with the female X chromosome.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe RNA-binding protein Sex-lethal (Sxl) is a critical regulator of sexual differentiation and dosage compensation in Drosophila. This regulatory activity is a consequence of the ability of Sxl to bind uridine-rich RNA tracts involved in pre-mRNA splicing. Sxl contains two RNP consensus-type RNA-binding domains (RBDs). A structural study of a portion of Sxl (amino acids 199-294) containing the second RNA-binding domain (RBD-2) using multidimensional heteronuclear NMR is presented here. Nearly complete 1H, 13C, and 15N resonance assignments have been obtained from 15N- and 13C/15N-uniformly labeled protein. These assignments were used to analyze 3D 15N-separated NOESY and 13C/13C-separated 4D NOESY spectra which produced 494 total and 169 long-range NOE-derived distance restraints. Along with 41 backbone dihedral restraints, these distance restraints were employed to generate an intermediate-resolution family of calculated structures, which exhibits the beta alpha beta-beta alpha beta tertiary fold found in other RBD-containing proteins. The RMSD to the average structure for the backbone atoms of residues 11-93 is 1.55 +/- 0.30 A, while the RMSD for backbone atoms involved in secondary structure is 0.76 +/- 0.14 A. A capping box [Harper, E.T., & Rose, G.D. (1993) Biochemistry 32, 7605-7609] was identified at the N-terminus of the first helix and has been characterized by short- and medium-range NOEs. Finally, significant structural similarities and differences between Sxl RBD-2 and other RBD-containing proteins are discussed. Resonance assignments and solution structure of the second RNA-binding domain of sex-lethal determined by multidimensional heteronuclear magnetic resonance.,Lee AL, Kanaar R, Rio DC, Wemmer DE Biochemistry. 1994 Nov 22;33(46):13775-86. PMID:7524663[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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