The research on transmembrane proteins (TMPs) is quite widespread due to their biological importance. Unfortunately, only a little amount of structural data is available of TMPs. Since technical difficulties arise during their high-resolution structure determination, bioinformatics and other experimental approaches are widely used to characterize their low-resolution structure, namely topology. Experimental and computational methods alone are still limited to determine TMP topology, but their combination becomes significant for the production of reliable structural data. By applying amino acid specific membrane-impermeable labelling agents, it is possible to identify the accessible surface of TMPs. Depending on the residue-specific modifications, new extracellular topology data is gathered, allowing the identification of more extracellular segments for TMPs. A new method has been developed for the experimental analysis of TMPs: covalent modification of the carboxyl groups on the accessible cell surface, followed by the isolation and digestion of these proteins. The labelled peptide fragments and their exact modification sites are identified by nanoLC-MS/MS. The determined peptides are mapped to the primary sequences of TMPs and the labelled sites are utilised as extracellular constraints in topology predictions that contribute to the refined low-resolution structure data of these proteins.
The β‐hairpin is a structural element of native proteins, but it is also a useful artificial scaffold for finding lead compounds to convert into peptidomimetics or non‐peptide structures for drug discovery. Since linear peptides are synthetically more easily accessible than cyclic ones, but are structurally less well‐defined, we propose XWXWXpPXK(/R)X(R) as an acyclic but still rigid β‐hairpin scaffold that is robust enough to accommodate different types of side chains, regardless of the secondary‐structure propensity of the X residues. The high conformational stability of the scaffold results from tight contacts between cross‐strand cationic and aromatic side chains, combined with the strong tendency of the d‐Pro‐l‐Pro dipeptide to induce a type II′ β‐turn. To demonstrate the robustness of the scaffold, we elucidated the NMR structures and performed molecular dynamics (MD) simulations of a series of peptides displaying mainly non‐β‐branched, poorly β‐sheet‐prone residues at the X positions. Both the NMR and MD data confirm that our acyclic β‐hairpin scaffold is highly versatile as regards the amino‐acid composition of the β‐sheet face opposite to the cationic−aromatic one.
Analysis of the NWA 2086 CV3 chondrite showed a matrix/chondrule ratio of 52%, similar to Bali, Mokoia, and Grosanaja. Nearly twice as many chondrule fragments as intact ones demonstrate that an early fragmentation phase occurred prior to final accretion. After this event, no substantial mechanical change or redeposition is evident. Rims with double‐layered structures were identified around some chondrules, which, in at least one case, is attributed to an accretionary origin. The rim's outer parts with a diffuse appearance were formed by in situ chemical alteration. During this later process, Mg content decreased, Fe content increased, and olivine composition was homogenized, producing a rim composition close to that of the matrix. This alteration occasionally happened along fractures and at confined locations, and was probably produced by fluid interactions. Iron oxides are the best candidate for a small grain‐sized alteration product; however, technical limitations in the available equipment did not allow exact phase identification. These results suggest that NWA 2086 came from a location (possible more deeply buried) in the CV parent body than Mokoia or Bali, and suffered less impact effects—although there is no evidence of sustained thermal alteration. This meteorite may represent a sample of the CV parent asteroid interior and provide a useful basis for comparison with other CV meteorites in the future.
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