Structural model for differential cap maturation at growing microtubule ends
Microtubules (MTs) are hollow cylinders made of tubulin, a GTPase responsible for essential functions during cell growth and division, and thus, key target for anti-tumor drugs. In MTs, GTP hydrolysis triggers structural changes in the lattice, which are responsible for interaction with regulatory factors. The stabilizing GTP-cap is a hallmark of MTs and the mechanism of the chemical-structural link between the GTP hydrolysis site and the MT lattice is a matter of debate. We have analyzed the structure of tubulin and MTs assembled in the presence of fluoride salts that mimic the GTP-bound and GDP •Pi transition states. Our results challenge current models because tubulin does not change axial length upon GTP hydrolysis. Moreover, analysis of the structure of MTs assembled in the presence of several nucleotide analogues and of taxol allows us to propose that previously described lattice expansion could be a post-hydrolysis stage involved in Pi release.
Authors: Zhylkaidarova A, Kaidarova D, Batyrbekov K, Shatkovskaya O, Begimbetova D Abstract We carried out an analysis of the total incidence of colon cancer throughout Kazakhstan. Retrospectively, according to the regional reports on endoscopic screening, the study showed an increase in the age-related incidence of colorectal cancer (CRC) cases from 2004-2008 to 2009-2014. The peak of morbidity in both periods was noted in the age category of>70 years. The indicators of the territorial distribution of CRC incidence make it possible to divide the regions into areas with low or high rates of CRC. Specific indicat...
Conclusions: The transduodenal approach for obtaining samples from solid lesions using a 19-G flexible needle seems feasible and accurate. PMID: 32447874 [PubMed - as supplied by publisher]