2JZ0

DSX_short

Summary for 2JZ0

• Entry DOI: 10.2210/pdb2jz0/pdb
• Related: 2JZ1
• Descriptor: Protein doublesex (1 entity in total)
• Functional Keywords: double sex, sex determination, development, gene regulation, ubiquitin, transcription
• Biological source: Drosophila melanogaster (fruit fly)
• Cellular location: Nucleus: P23023
• Total number of polymer chains: 2
• Total formula weight: 15491.47

Authors

Yang, Y.,Zhang, W.,Bayrer, J.R.,Weiss, M.A. (deposition date: 2007-12-21, release date: 2008-01-08, Last modification date: 2024-05-29)

Primary citation

Yang, Y.,Zhang, W.,Bayrer, J.R.,Weiss, M.A.
Doublesex and the Regulation of Sexual Dimorphism in Drosophila melanogaster: STRUCTURE, FUNCTION, AND MUTAGENESIS OF A FEMALE-SPECIFIC DOMAIN.
J.Biol.Chem., 283:7280-7292, 2008

PubMed 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 highlights the importance of steric and electrostatic complementarity across the interface. Two temperature-sensitive mutations at this interface have been characterized in yeast model systems. One weakens a network of solvated salt bridges, whereas the other perturbs the underlying nonpolar interface. These mutations confer graded gene-regulatory activity in yeast within a physiological temperature range and so may provide novel probes for genetic analysis of a sex-specific transcriptional program in Drosophila development.

PubMed: 18184648
DOI: 10.1074/jbc.M708742200

Experimental method

SOLUTION NMR