Doublesex and the regulation of sexual dimorphism in Drosophila melanogaster: structure, function, and mutagenesis of a female-specific domain

The Journal of Biological Chemistry
Yanwu YangMichael A Weiss

Abstract

The DSX (Doublesex) transcription factor regulates somatic sexual differentiation in Drosophila. Female and male isoforms (DSX F and DSX M) are formed due to sex-specific RNA splicing. DNA recognition, mediated by a shared N-terminal zinc module (the DM domain), is enhanced by a C-terminal dimerization element. Sex-specific extension of this element in DSX F and DSX M leads to assembly of distinct transcriptional preinitiation complexes. Here, we describe the structure of the extended C-terminal dimerization domain of DSX F as determined by multidimensional NMR spectroscopy. The core dimerization element is well ordered, giving rise to a dense network of interresidue nuclear Overhauser enhancements. The structure contains dimer-related UBA folds similar to those defined by x-ray crystallographic studies of a truncated domain. Whereas the proximal portion of the female tail extends helix 3 of the UBA fold, the distal tail is disordered. Ala substitutions in the proximal tail disrupt the sex-specific binding of IX (Intersex), an obligatory partner protein and putative transcriptional coactivator; IX-DSX F interaction is, by contrast, not disrupted by truncation of the distal tail. Mutagenesis of the UBA-like dimer of DSX F highli...Continue Reading

References

Aug 17, 1989·Nature·B S Baker
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·J M Belote, B S Baker
Jan 1, 1981·Molecular & General Genetics : MGG·M Bownes, R Nöthiger
Dec 1, 1994·Protein Science : a Publication of the Protein Society·L Jin, J A Wells
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Feb 1, 1996·Journal of Molecular Graphics·R KoradiK Wüthrich
Jan 1, 1996·Annual Review of Genetics·T W Cline, B J Meyer
Feb 7, 1997·The Journal of Biological Chemistry·S Cho, P C Wensink
Feb 1, 1997·Nature Structural Biology·J G OmichinskiG M Clore
Mar 7, 1998·Nature·C S RaymondD Zarkower
Aug 26, 1998·The EMBO Journal·M CaffreyG M Clore
Nov 4, 1998·Current Biology : CB·B I ArthurR Nöthiger
Jun 17, 2000·Science·Y S Rong, K G Golic
Jul 6, 2000·Science·W R Engels
Dec 22, 2000·Genes & Development·J Zhu, A R Krainer
Aug 9, 2001·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·L Sánchez, I Guerrero
Aug 30, 2001·Cell·S VincentN Perrimon
Jun 25, 2002·Journal of Molecular Biology·Thomas D Mueller, Juli Feigon
Aug 29, 2002·The Journal of Biological Chemistry·Uma NarendraMichael A Weiss
Dec 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·Doo-Byoung OhAlexander Rich
Feb 5, 2003·Journal of Magnetic Resonance·Charles D SchwietersG Marius Clore
Jun 24, 2004·Acta Crystallographica. Section D, Biological Crystallography·James BayrerMichael A Weiss
Jun 7, 2005·Cell·Ebru Demir, Barry J Dickson

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Jul 30, 2021·Molecular Biology and Evolution·Fernando Rodriguez-CaroBrian A Counterman

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