A. thaliana Cobalamin - Independent Methionine Synthase X-ray structure courtesy of RCSB/Protein Data Bank.
Biology
Dartmouth researchers discover a protein methylation pathway in Chlamydomonas flagella
Cobalamin-independent methionine synthase (MetE), a flagellar protein in Chlamydomonas, has been discovered as a key component to the assembly and/or disassembly of the cellular flagellum, as reported by Dartmouth researchers Roger Sloboda, Megan Ulland, and Mark Schneider in Molecular Biology of the Cell in October.
Recent research shows that MetE also functions in the flagella as a catalyst of the reaction of homocysteine into methionine. Methionine when converted into S-adenosyl methionine (SAM) is a component of the flagellar proteome. Because SAM is the methyl donor for methylating proteins, MetE is directly related to the production of these proteins. Low amounts of MetE were found in full-length flagella, increased amounts in regenerating flagella, and highest amounts in resorbing flagella suggesting a link between flagellar protein methylation and the cellular cycle.
For the first time, protein methylation at arginine residues is being shown to be concurrent with flagellar resorption, proving that it is important for more than just gene transcription. It “may be a necessary step in the disassembly of axonemal structures or required to promote the association of disassembled axonemal proteins,” the team stated in their article. The coinciding of protein methylation with flagellar resorption, a step that takes place before cellular division, is the gateway to further studies on the linkage between flagellar protein methylation and cell cycle progression. (1)
Link found between Drosophila CheB gene expression and Tay-Sachs disease
Recently, the protein CheB42a in Drosophila was found to be a regulator of progression into late stages of male courtship. This finding has been the platform for studies involving other CheB genes and their connection to the function of the GM2-Activator Protein (GM2-AP) in humans. Claudio Pikielny of Dartmouth Medical School has concluded that CheB’s function in pheromone response might include biochemical mechanisms important to lipid metabolism in human neurons. Mutated versions of CheB42a in Drosophila exhibited results suggesting its functioning in gustatory perception of female cuticular hydrocarbon pheromones, the team reported in the Journal of Biological Chemistry in October. Because of this, genes in the CheB series were investigated to pinpoint the underlying mechanism.
DNA database searches revealed that there were sequence similarities between CheBs, CheBrs, and the human GM2-AP, a member of the myeloid differentiation protein-like (ML) superfamily. The sequence similarities between these genes mean that all three bind to similar chemical ligands. This and the fact that CheB falls under the domain of a lipid binding protein, hints that CheB function in gustatory perception of the lipid-like pheromones of Drosophila is related to the critical steps of lipid metabolism.
Human GM2-AP loss in Tay-Sachs disease results in neurodegeneration by inhibiting GM2 ganglioside degradation. Hence, it is suggested that CheBs function in pheromone response might include the biochemical mechanisms critical for lipid metabolism in human neurons. Research is continuing in Pikielny’s lab as more data about the CheBs function and detection of lipid-like pheromones of Drosophila might elucidate new aspects of human lipid metabolism. (2)
Physiology & Medicine
The hazards of smoking taken to a new level
The dangers of firsthand and secondhand smoke are well known to the public. However, a recent study published in Pediatrics, conducted in part by DMS professor Susanne Tanski, has brought attention to another deleterious consequence of smoking: “thirdhand” smoke. Thirdhand smoke is defined as the residual toxins that remain in a room or on the body of a smoker long after initial exposure to tobacco smoke. These toxins include compounds such as hydrogen cyanide, toluene, carbon monoxide, arsenic, lead, butane, and even radioactive polonium-210, and many of them are carcinogenic.
Thirdhand smoke is particularly harmful to children, who are more vulnerable to even small amounts of its contaminants. This is particularly true of infants whose propensity for physical contact with objects increases the number of instances in which they will ingest or inhale thirdhand smoke. The article further notes that “cognitive deficits,” such as lower reading scores, have in previous studies been associated with exposure to toxins of thirdhand smoke.
The study, designed as a survey of 1510 households, was conducted by the American Academy of Pediatrics. The goal was to observe the possible relationship between knowledge of thirdhand smoke’s effects and the household bans on smoking. Results suggested that those who are more informed about the vices of thirdhand smoke may be more inclined to ban smoking from their homes. However, the incorporation of thirdhand smoke in anti-tobacco campaigns is yet to be seen. (3)
A new protein function revealed cell division mechanisms
NOD-Microtubule-Chromosome illustration courtesy of Jared Cochran.
A new function was discovered for the Drosophila protein NOD that sheds light on the intricate mechanics of cell division, Dartmouth College chemistry professor F. Jon Kull reported with his research team early this month in Cell. When chromosomes do not segregate correctly in cell division, complications can arise as in the case of cancerous cells.
The protein NOD is distantly related to motor proteins that drive cellular activities like transport and cell division. Though NOD itself lacks the capacity for movement along microtubules (MTs), it stimulates microtubule polymerization, highlighting its importance in chromosome segregation. Found in fruit flies, the NOD protein will help determine how related proteins in humans work.
With their recent findings, the researchers were able to propose an in vivo model for NOD function. “This work describes a novel mode for kinesin function, in which NOD does not walk, but rather alternates between grabbing on to and letting go of the end of the growing filament, thereby tracking the end as it grows. The diversity of function of these proteins is remarkable,” said Kull in the press release.
The research is at the frontier in providing a better understanding of the mechanics of cell division, one of the key components of life. (4)
Computer Science
Algorithm developed to approximate polygonal curves
Dartmouth computer science professor Scot Drysdale and his research team published a computer algorithm for constructing a graph of all possible arcs as well as of polygonal curve approximation in Computational Geometry last March. The algorithm’s components include concepts of circular ray shooting, tolerance boundaries, and the Voronoi diagram.
In the paper, Drysdale outlines the process leading up to the application of the algorithm. A bisector ray is intersected with an intersection of two wedges, regions of the centers of the disks, and a Voronoi region. The goal behind this is to see if the two intersections overlap. A gate is included at every vertex to avoid overshooting the bend and the uncertainty accompanied with whether the curve will stay close to designated points in regions consisting of sharp corners.
Biarcs, segments consisting of pairs of circular arcs, became important when the team realized that they could make calculating the second arc symmetric to calculating the first if they reversed the direction of the second arc and its tangent. Biarcs respecting the tangent directions at the original points is the means in which the algorithm interjects between a newly chosen subsequence of input points.
In the future, Drysdale and his colleagues hope to find algorithms without as many restrictions. This would enable the study of biarcs or arcs that end at different points than they began. (5)
References
1. M. J. Schneider, M. Ulland, R. D. Sloboda, Mol. Biol. Cell 19, 4319–4327 (2008).
2. E. Starostina, A. Xu, H. Lin, C. W. Pikielny, J. Biol. Chem. 284, 585-594 (2009).
3. J. P. Winickoff et al., Pediatrics 123, e74-e79 (2008).
4. J. C. Cochran et al., Cell 136, 110-122 (2009).
5. R. L. S. Drysdale, G. Rote, A. Sturm, Comp. Geom. 41, 31-47 (2008).