73 research outputs found
How Cations Change Peptide Structure
Specific interactions between cations and proteins have a strong impact on
peptide and protein structure. We here shed light on the nature of the
underlying interactions, especially regarding the effects on the polyamide
backbone structure. To do so, we compare the conformational ensembles of model
peptides in isolation and in the presence of either Li+ or Na+ cations by
state-of-the-art density-functional theory (including van der Waals effects)
and gas-phase infrared spectroscopy. These monovalent cations have a drastic
effect on the local backbone conformation of turn-forming peptides, by
disruption of the H bonding networks and the resulting severe distortion of the
backbone conformations. In fact, Li+ and Na+ can even have different
conformational effects on the same peptide. We also assess the predictive power
of current approximate density functionals for peptide-cation systems and
compare to results from established protein force fields as well as to
high-level quantum chemistry (CCSD(T)).Comment: 30 pages, 7 figure
Exploring the conformational preferences of 20-residue peptides in isolation: Ac-Ala 19
Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.
We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis
Duration features in prosodic classification: why normalization comes second, and what they really encode
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