Tuesday, November 25, 2008

Compasses, Translational Machinery and a little epigenetics

A few more agents and biomolecular machines .
Protein Compass Guides Amoebas Toward Their Prey
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ScienceDaily (Oct. 26, 2008) — Amoebas glide toward their prey with the help of a protein switch that controls a molecular compass, biologists at the University of California, San Diego have discovered.
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Their finding, recently detailed in the journal Current Biology, is important because the same molecular switch is shared by humans and other vertebrates to help immune cells locate the sites of infections.

The amoeba Dictyostelium finds bacteria by scent and moves toward its meal by assembling a molecular motor on its leading edge. The active form of a protein called Ras sets off a cascade of signals to start up that motor, but what controlled Ras was unknown.

Richard Firtel, professor of biology along with graduate student Sheng Zhang and postdoctoral fellow Pascale Charest tested seven suspect proteins by disrupting their genes. One called NF1, which matches a human protein, proved critical to chemical navigation.

NF1 turns Ras off. Without this switch mutant amoebas extended false feet called pseudopodia in all directions and wandered aimlessly as Ras flickered on and off at random points on their surfaces. “You have to orient Ras in order to drive your cell in the right direction,” Firtel said.

In contrast, normal amoebas with working versions of NF1 elongate in a single direction and head straight for the most intense concentration of bacterial chemicals, the team reports.

The biochemical components of the system match those found in vertebrate immune cells called neutrophils that hunt down bacterial invaders, suggesting that the switch might be a key navigational control for many types of cells, Firtel said. “The pathway and responses are very similar and so are the molecules.

The US Public Health Service funded this work.
Agents assemble their equipment in order to hunt down their prey. An intentional plan laid out purposefully in order to manipulate the environment as a means to an end... food.


More equipment capable of manipulating the environment as a means to an end....
New Light Shed On Molecular Machinery Required For Translation Of Histone Crosstalk
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ScienceDaily (Dec. 14, 2007) — The Stowers Institute's Shilatifard Lab has published findings that shed light on the molecular machinery required for the translation of histone crosstalk, or communication between histones.
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Histones are important components of chromatin, the packing material surrounding chromosomal DNA. Also, histones play an important role in the regulation of gene expression. Histone H3 can be modified by methylation and this modification is an essential part of gene expression.

Several years ago, the Shilatifard Lab identified the first histone H3 lysine 4 (H3K4) methyltransferase, known as COMPASS, in yeast. Soon thereafter, it was established that the MLL protein in humans also existed in a COMPASS-like complex capable of methylating H3K4. In 2002, the Shilatifard Lab reported the existence of the first histone crosstalk between histone H2B monoubiquitination for the regulation of histone methylation by COMPASS.

"We now know that this mode of histone crosstalk is highly conserved from yeast to humans, but until now, its molecular mechanism of action was poorly understood. Jung-Shin Lee, a Postdoctoral Research Associate in my laboratory, was able to demonstrate the molecular machinery required for the translation of this histone crosstalk," said Ali Shilatifard, Ph.D., Investigator and senior author on the paper.

This work demonstrated that the Cps35 subunit of COMPASS is required to translate the crosstalk between H2B monoubiquitination and H3 methylation by COMPASS.

"Given the importance of histone methylation by the MLL complex and leukemia pathogenesis, defining the molecular machinery involved in this process could be highly useful," said Dr. Shilatifard.

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