抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Molecular mechanics is powerful for its speed in atomistic simulations, but an accurate force field is required. The Amber ff99SB force field improved protein secondary structure balance and dynamics from earlier force fields like ff99, but weaknesses in side chain rotamer and backbone secondary structure preferences have been identified. Here, we performed a complete refit of all amino acid side chain dihedral parameters, which had been carried over from ff94. The training set of conformations included multidimensional dihedral scans designed to improve transferability of the parameters. Improvement in all amino acids was obtained as compared to ff99SB. Parameters were also generated for alternate protonation states of ionizable side chains. Average errors in relative energies of pairs of conformations were under 1.0 kcal/mol as compared to QM, reduced 35% from ff99SB. We also took the opportunity to make empirical adjustments to the protein backbone dihedral parameters as compared to ff99SB. Multiple sm...

/pdf/ff14sb-improving-the-accuracy-of-protein-side-chain-and-2f0ci0lvo5.pdf

ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB

Peptides or proteins convert under some conditions from their soluble forms into highly ordered fibrillar aggregates. Such transitions can give rise to pathological conditions ranging from neurodegenerative disorders to systemic amyloidoses. In this review, we identify the diseases known to be associated with formation of fibrillar aggregates and the specific peptides and proteins involved in each case. We describe, in addition, that living organisms can take advantage of the inherent ability of proteins to form such structures to generate novel and diverse biological functions. We review recent advances toward the elucidation of the structures of amyloid fibrils and the mechanisms of their formation at a molecular level. Finally, we discuss the relative importance of the common main-chain and side-chain interactions in determining the propensities of proteins to aggregate and describe some of the evidence that the oligomeric fibril precursors are the primary origins of pathological behavior.

/pdf/protein-misfolding-functional-amyloid-and-human-disease-2w386pwb7k.pdf

Protein Misfolding, Functional Amyloid, and Human Disease

The influence of diet on the distribution of nitrogen isotopes in animals was investigated by analyzing animals grown in the laboratory on diets of constant nitrogen isotopic composition. 
The isotopic composition of the nitrogen in an animal reflects the nitrogen isotopic composition of its diet. The δ^(15)N values of the whole bodies of animals are usually more positive than those of their diets. Different individuals of a species raised on the same diet can have significantly different δ^(15)N values. The variability of the relationship between the δ^(15)N values of animals and their diets is greater for different species raised on the same diet than for the same species raised on different diets. Different tissues of mice are also enriched in ^(15)N relative to the diet, with the difference between the δ^(15)N values of a tissue and the diet depending on both the kind of tissue and the diet involved. The δ^(15)N values of collagen and chitin, biochemical components that are often preserved in fossil animal remains, are also related to the δ^(15)N value of the diet. 
The dependence of the δ^(15)N values of whole animals and their tissues and biochemical components on the δ^(15)N value of diet indicates that the isotopic composition of animal nitrogen can be used to obtain information about an animal's diet if its potential food sources had different δ^(15)N values. The nitrogen isotopic method of dietary analysis probably can be used to estimate the relative use of legumes vs non-legumes or of aquatic vs terrestrial organisms as food sources for extant and fossil animals. However, the method probably will not be applicable in those modern ecosystems in which the use of chemical fertilizers has influenced the distribution of nitrogen isotopes in food sources. 
The isotopic method of dietary analysis was used to reconstruct changes in the diet of the human population that occupied the Tehuacan Valley of Mexico over a 7000 yr span. Variations in the δ^(15)C and δ^(15)N values of bone collagen suggest that C_4 and/or CAM plants (presumably mostly corn) and legumes (presumably mostly beans) were introduced into the diet much earlier than suggested by conventional archaeological analysis.

Influence of Diet On the Distribtion of Nitrogen Isotopes in Animals

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

The V3-loop is an immunodominant region within the envelope protein of HIV-1. Peptides of this region are used to classify HIV-1 into subtypes based on the seroreactivity of patients’ sera. However, correlation between genetically determined subtypes and their seroreactivity is not yet fully established. Therefore, new approaches have been pursued [1]. We evaluated the immunological reactivity of polyclonal human anti-HIV antibodies from patient sera against a solid phase decapeptide library derived from HIV-1 V3 sequence data in order to achieve a minimal set of peptides with orthogonal seroreactivites against different subtypes. This approach serves as a basis to establish an immunofluorescence based assay for subtyping HIV-1.

Towards a Set of Peptides with Orthogonal HIV Seroreactivity Using Adaptively Coded Peptide Libraries: Decoding by Mass Spectrometry and Immunofluorescent Screening

The high-power impulse magnetron sputtering (HiPIMS) technique was applied to deposit multilayer-like (Cr, Y)Nx coatings on AISI 304L stainless steel, using pendular substrate oscillation and a Cr-Y target and varying the nitrogen flow rate from 10 to 50 sccm. The microstructure, mechanical and tribological properties were investigated by scanning and transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, instrumented nano-hardness, and wear tests. The columnar grain structure became highly segmented and nanosized due to pendular substrate oscillation and the addition of yttrium. The deposition rate increased continuously with the growing nitrogen flow rate. The increase in nitrogen flow from 10 to 50 sccm increased the hardness of the coatings (Cr, Y)Nx, with a maximum hardness value of 32.7 GPa for the coating (Cr, Y)Nx with a nitrogen flow of 50 sccm, which greatly surpasses the hardness of CrN films with multilayer-like (Cr, Y)Nx coatings architecture. The best mechanical and tribological performance was achieved for a nitrogen flow rate of 50 sccm. This was enabled by more elevated compressive stresses and impact energies of the impinging ions during film growth, owing to an increase of HiPIMS peak voltage with a rising N2/Ar ratio.

/pdf/role-of-nitrogen-and-yttrium-contents-in-manufacturing-cr-y-3oc4vbpb.pdf

Role of Nitrogen and Yttrium Contents in Manufacturing (Cr, Y)Nx Film Nanostructures

NMR Spectroscopic Elucidation of Constitutions of Glycopeptides by the COLOC Technique.

Optical investigations of nanometer distances between proteins, their subunits, or other biomolecules have been the exclusive prerogative of Förster Resonance Energy Transfer (FRET) microscopy for decades. Here we show that MINFLUX fluorescence nanoscopy measures intra-molecular distances down to 1 nm – and in planar projections down to 1 Angström – directly, linearly, and with Angström precision. Our method is validated by quantifying well-characterized 1-to-10 nm distances in polypeptides and proteins. Moreover, we visualize the orientations of immunoglobulin subunits and reveal specific configurations of a histidine kinase domain dimer. Our results open the door for examining proximities and interactions of macromolecules under physiological conditions.

/pdf/direct-optical-measurement-of-intra-molecular-distances-down-1ftr6b7b.pdf

Christian Griesinger

Papers

Towards a Set of Peptides with Orthogonal HIV Seroreactivity Using Adaptively Coded Peptide Libraries: Decoding by Mass Spectrometry and Immunofluorescent Screening

Role of Nitrogen and Yttrium Contents in Manufacturing (Cr, Y)Nx Film Nanostructures

NMR Spectroscopic Elucidation of Constitutions of Glycopeptides by the COLOC Technique.

Direct optical measurement of intra-molecular distances down to the Ångström scale

FAST NOESY — ein Ansatz zur schnelleren Strukturbestimmung†