4B7Y

Crystal structure of the MSL1-MSL2 complex

Summary for 4B7Y

• Entry DOI: 10.2210/pdb4b7y/pdb
• Descriptor: MALE-SPECIFIC LETHAL 1 HOMOLOG, MALE-SPECIFIC LETHAL 2 HOMOLOG, ZINC ION (3 entities in total)
• Functional Keywords: gene regulation, dosage compensation, chromatin
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: Q68DK7
• Total number of polymer chains: 4
• Total formula weight: 36385.55

Authors

Hallacli, E.,Lipp, M.,Georgiev, P.,Spielman, C.,Cusack, S.,Akhtar, A.,Kadlec, J. (deposition date: 2012-08-24, release date: 2013-02-06, Last modification date: 2023-12-20)

Primary citation

Hallacli, E.,Lipp, M.,Georgiev, P.,Spielman, C.,Cusack, S.,Akhtar, A.,Kadlec, J.
Msl1-Mediated Dimerization of the Dosage Compensation Complex is Essential for Male X-Chromosome Regulation in Drosophila.
Mol.Cell, 48:587-, 2012

PubMed Abstract: The Male-Specific Lethal (MSL) complex regulates dosage compensation of the male X chromosome in Drosophila. Here, we report the crystal structure of its MSL1/MSL2 core, where two MSL2 subunits bind to a dimer formed by two molecules of MSL1. Analysis of structure-based mutants revealed that MSL2 can only interact with the MSL1 dimer, but MSL1 dimerization is MSL2 independent. We show that Msl1 is a substrate for Msl2 E3 ubiquitin ligase activity. ChIP experiments revealed that Msl1 dimerization is essential for targeting and spreading of the MSL complex on X-linked genes; however, Msl1 binding to promoters of male and female cells is independent of the dimer status and other MSL proteins. Finally, we show that loss of Msl1 dimerization leads to male-specific lethality. We propose that Msl1-mediated dimerization of the entire MSL complex is required for Msl2 binding, X chromosome recognition, and spreading along the X chromosome.

PubMed: 23084835
DOI: 10.1016/J.MOLCEL.2012.09.014

Experimental method

X-RAY DIFFRACTION (3.25 Å)