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EMBL News

Grenoble, 26 October 2012

The proteins came in two by two

Protein pairing essential for male fruit fly survival

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Two copies of the MSL1 protein pair up, and serve as a docking-point for 2 copies of MSL2.
Credit: EMBL/J. Kadlec

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Female fruit flies have two copies of the X chromosome, while males – whose other sex chromosome is a Y – have only one. Scientists at EMBL Grenoble, together with researchers from the Max Plank Institute for Immunobiology and Epigenetics in Freiburg, Germany, discovered that, for the male flies to be able to make up for this shortage, 2 copies of a particular protein called Msl1 have to pair up. Their study was published this month in Molecular Cell.

To compensate for having just one copy of the X-chromosome, the male fruit fly makes the genes on that chromosome work twice as hard. This increased output is triggered by a set of proteins that assemble into a cellular machine called Male-Specific Lethal (MSL) complex. So far, scientists didn’t know exactly how the MSL machinery recognises the X-chromosome and cranks up its output, but Jan Kadlec, from Stephen Cusack’s group at EMBL Grenoble, and EMBL alumna Asifa Akhtar, now at MPI Freiburg, have identified a key step in this process.

Jan determined the 3-dimensional structure of two MSL proteins, Msl1 and Msl2. He unexpectedly found that two copies of MSL1 first have to pair up, and that pair then serves as a docking-point for 2 copies of MSL2, which attach themselves one to either side of it. This means that, in all likelihood, all 5 proteins in the MSL machinery come in pairs, making the complex two times bigger than scientists thought.

“Now we know the structure, we can identify individual mutations which you can use to surgically remove different subunits from the complex, and this I think is really a great tool for the field,” says Jan. Asifa’s group did exactly that for MSL1 and MSL2, and discovered that the whole MSL machine only assembles properly if the MSL1 proteins pair up, but for this machinery to find and act upon the X chromosome, MSL2 also has to be in place.

The scientists have already probed other parts of the MSL machinery in this way, and hope to see the approach extended to provide a complete picture of how MSL accomplishes its vital role.

 

Further information

Jan, Stephen and Asifa’s work on other MSL components

Source Article

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. Molecular Cell, 18 October 2012. DOI:10.1016/j.molcel.2012.09.014.