Protein folding on the ribosome studied using NMR spectroscopy

NMR spectroscopy is a powerful tool for the investigation of protein folding and misfolding, providing a characterization of molecular structure, dynamics and exchange processes, across a very wide range of timescales and with near atomic resolution. In recent years NMR methods have also been developed to study protein folding as it might occur within the cell, in a de novo manner, by observing the folding of nascent polypeptides in the process of emerging from the ribosome during synthesis. Despite the 2.3 MDa molecular weight of the bacterial 70S ribosome, many nascent polypeptides, and some ribosomal proteins, have sufficient local flexibility that sharp resonances may be observed in solution-state NMR spectra. In providing information on dynamic regions of the structure, NMR spectroscopy is therefore highly complementary to alternative methods such as X-ray crystallography and cryo-electron microscopy, which have successfully characterized the rigid core of the ribosome particle. However, the low working concentrations and limited sample stability associated with ribosome-nascent chain complexes means that such studies still present significant technical challenges to the NMR spectroscopist. This review will discuss the progress that has been made in this area, surveying all NMR studies that have been published to date, and with a particular focus on strategies for improving experimental sensitivity

Stratum corneum lipid matrix with unusual packing: a molecular dynamics study

The skin is an effective barrier against the external elements being the stratum corneum, with its lipid matrix surrounding the corneocytes, considered the major player responsible for its low permeability. The use of computational models to study the transdermal delivery of compounds have a huge potential to improve this research area, but requires reliable models of the skin components. In this work, we developed molecular dynamics models with a coarse-grained resolution, of the stratum corneum lipid matrix and the sebum. We developed the lipid matrix model with unusual lipid packing configuration as some recent works support. The simulation results show that this configuration is stable and may help to explain the low permeability of stratum corneum. The sebum simulations showed that this oily skin product can also play a significant role in the transdermal delivery of drugs.We thank the Portuguese Foundation for Science and Technology (FCT) for providing the grant for part of Egipto Antunes Ph.D. studies (scholarship SFRH/BD/122952/2016), and to also support this work under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. We want to thank the access of Minho University “SeARCH” ("Services and Advanced Research Computing with HTC/HPC clusters") cluster. We also thank Tarsila Castro for its technical advice and text revision.info:eu-repo/semantics/publishedVersio