Modeling a disease-correlated tubulin mutation in budding yeast reveals insight into MAP-mediated dynein function.

Mutations in the genes that encode α- and ß-tubulin underlie many neurological diseases, most notably malformations in cortical development. In addition to revealing the molecular basis for disease etiology, studying such mutations can provide insight into microtubule function and the role of the large family of microtubule effectors. In this study, we use budding yeast to model one such mutation-Gly436Arg in α-tubulin, which is causative of malformations in cortical development-in order to understand how it impacts microtubule function in a simple eukaryotic system. Using a combination of in vitro and in vivo methodologies, including live cell imaging and electron tomography, we find that the mutant tubulin is incorporated into microtubules, causes a shift in α-tubulin isotype usage, and dramatically enhances dynein activity, which leads to spindle-positioning defects. We find that the basis for the latter phenotype is an impaired interaction between She1-a dynein inhibitor-and the mutant microtubules. In addition to revealing the natural balance of α-tubulin isotype utilization in cells, our results provide evidence of an impaired interaction between microtubules and a dynein regulator as a consequence of a tubulin mutation and sheds light on a mechanism that may be causative of neurodevelopmental diseases.

Looking for the PC bond in space: HPCO and HPCS as possible tracers.

This paper looks at the possibility of astronomical detection of molecules of prebiotic interest containing phosphorus. Attention has been focused on the most stable species that can be formed with the four [C,H,O,P] atoms. Ab initio coupled cluster molecular orbital methods and density functional theory have been used. It is found that the best candidate for detection is singlet HPCO (corresponding to singlet HNCO), which lies 23.5 kcal/mol lower than the next isomer (HOCP) and has a non-negligible dipole moment of 0.8 D. Theoretical rotational constants and infrared (IR) spectra have been determined for HPCO and the closely related HPCS. By correcting the known inadequacies in the calculations with the average theoretical to experimental ratio from two benchmark molecules (HOCO+ and HNCO), it is possible to obtain rotational constants and IR frequencies of considerably higher accuracy. The corrected values of B = 5.5322 GHz and C = 5.4071 GHz for HPCO, and B = 3.0416 GHz and C = 3.0014 GHz for HPCS should be accurate to within a few tenths of a percent. It can also be predicted that only the 2000 cm(-1) (HPCO) and 1400 cm(-1) (HPCS) IR bands have sufficient intensity to be searched in the low-abundance conditions prevailing in space.

Potential Energy Curves and Electronic Structure of Copper Nitrides CuN and CuN+ Versus CuO and CuO+

Ab initio configuration interaction calculations for the diatomic CuO, CuN, CuO+, and CuN+ have been carried out, and potential energy curves are reported for several low-lying states of these systems. The electronic structure and bonding, not yet known for the neutral copper nitride and its cation, are examined and compared to those of the copper oxide systems. We find that the ground states of these systems are X2Pi (CuO), X3Sigma- (CuN), X3Sigma- (CuO+), and X4Sigma- (CuN+); their first low-lying excited states Y2Sigma+, 1Delta, 1Delta, and 2Pi are located at 0.69, 1.45, 2.32, and 2.09 eV, respectively. For CuO we found two unobserved quartet states, namely 4Sigma- (Te = 1.09 eV) and 4Pi (Te = 1.86 eV). We report equilibrium structural parameters for various electronic states of the studied systems and compare them with experimental values, where it is possible. Copyright 1999 Academic Press.