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

J. Appl. Cryst.の発刊に際して

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

Marine natural products.

Geometrical validation around the Calpha is described, with a new Cbeta measure and updated Ramachandran plot. Deviation of the observed Cbeta atom from ideal position provides a single measure encapsulating the major structure-validation information contained in bond angle distortions. Cbeta deviation is sensitive to incompatibilities between sidechain and backbone caused by misfit conformations or inappropriate refinement restraints. A new phi,psi plot using density-dependent smoothing for 81,234 non-Gly, non-Pro, and non-prePro residues with B < 30 from 500 high-resolution proteins shows sharp boundaries at critical edges and clear delineation between large empty areas and regions that are allowed but disfavored. One such region is the gamma-turn conformation near +75 degrees,-60 degrees, counted as forbidden by common structure-validation programs; however, it occurs in well-ordered parts of good structures, it is overrepresented near functional sites, and strain is partly compensated by the gamma-turn H-bond. Favored and allowed phi,psi regions are also defined for Pro, pre-Pro, and Gly (important because Gly phi,psi angles are more permissive but less accurately determined). Details of these accurate empirical distributions are poorly predicted by previous theoretical calculations, including a region left of alpha-helix, which rates as favorable in energy yet rarely occurs. A proposed factor explaining this discrepancy is that crowding of the two-peptide NHs permits donating only a single H-bond. New calculations by Hu et al. [Proteins 2002 (this issue)] for Ala and Gly dipeptides, using mixed quantum mechanics and molecular mechanics, fit our nonrepetitive data in excellent detail. To run our geometrical evaluations on a user-uploaded file, see MOLPROBITY (http://kinemage.biochem.duke.edu) or RAMPAGE (http://www-cryst.bioc.cam.ac.uk/rampage).

Structure validation by Calpha geometry: phi,psi and Cbeta deviation.

T e purpose of this review is to assess the nature and magnitudes of the dominant forces in protein folding. Since proteins are only marginally stable at room temperature,’ no type of molecular interaction is unimportant, and even small interactions can contribute significantly (positively or negatively) to stability (Alber, 1989a,b; Matthews, 1987a,b). However, the present review aims to identify only the largest forces that lead to the structural features of globular proteins: their extraordinary compactness, their core of nonpolar residues, and their considerable amounts of internal architecture. This review explores contributions to the free energy of folding arising from electrostatics (classical charge repulsions and ion pairing), hydrogen-bonding and van der Waals interactions, intrinsic propensities, and hydrophobic interactions. An earlier review by Kauzmann (1959) introduced the importance of hydrophobic interactions. His insights were particularly remarkable considering that he did not have the benefit of known protein structures, model studies, high-resolution calorimetry, mutational methods, or force-field or statistical mechanical results. The present review aims to provide a reassessment of the factors important for folding in light of current knowledge. Also considered here are the opposing forces, conformational entropy and electrostatics. The process of protein folding has been known for about 60 years. In 1902, Emil Fischer and Franz Hofmeister independently concluded that proteins were chains of covalently linked amino acids (Haschemeyer & Haschemeyer, 1973) but deeper understanding of protein structure and conformational change was hindered because of the difficulty in finding conditions for solubilization. Chick and Martin (191 1) were the first to discover the process of denaturation and to distinguish it from the process of aggregation. By 1925, the denaturation process was considered to be either hydrolysis of the peptide bond (Wu & Wu, 1925; Anson & Mirsky, 1925) or dehydration of the protein (Robertson, 1918). The view that protein denaturation was an unfolding process was

/pdf/dominant-forces-in-protein-folding-42bjzlldw4.pdf

Dominant forces in protein folding

Structural characteristics of .alpha.-helical peptide molecules containing Aib residues

The construction of complex protein folds relies on the precise conversion of a linear polypeptide chain into a compact 3-dimensional structure. The interplay of forces that link sequence and folding is intricate and yet to be firmly elucidated. Examination of protein 3-dimensional structures suggests that complex tertiary folds and quaternary associations can be deconstructed into a limited number of secondary structural elements, such as strands, helices, and turns, which are assembled using loosely structured loops (Figure 1). The stability of a specific fold is determined by tertiary interactions between residues which are distant in sequence. De novo design of existing or novel protein folds demands a thorough understanding of the rules that underlie protein structure and stability.

/pdf/design-of-folded-peptides-3j8etv1eac.pdf

Design of folded peptides.

The introduction of alpha-aminoisobutyric acid (Aib) into peptides dramatically limits the range of accessible backbone conformations. The presence of two geminal methyl groups at C alpha sterically compels Aib residues to largely favor structures in the right- or left-handed 3(10)/alpha-helical regions (phi approximately +/- 60 +/- 20 degrees, psi approximately +/- 30 +/- 20 degrees) of the peptide conformational map. Aib residues occur extensively in microbial peptides which form transmembrane channels. This observation has stimulated considerable interest in the stereochemistry of Aib peptides. This review summarizes theoretical studies on the conformations of Aib residues and examines the available data on solid-state structures, derived from single crystal X-ray diffraction studies. Crystal structures of over three dozen Aib-containing peptides, ranging in length from 2 to 11 residues, have been reported so far which exemplify various types of beta-turns, consecutive beta-turns, and helical structures. Examples of nonhydrogen bonded and cyclic structures are also described. The crystallographic results compare well with structural studies in solution, establishing that Aib peptides can provide rigid structural models for the development of spectroscopic methods of peptide conformational analysis.

The stereochemistry of peptides containing alpha-aminoisobutyric acid.

6. ω Amino Acids in Hairpins 672 6.1. Insertion into Turn Segments 672 6.2. Extended Strands 673 7. Conformational Representations 673 7.1. Conformationally Constrained Residues 675 8. Conformational Variability and Biological Activity 677 8.1. Conformational Variability in Solution 677 8.2. Biological Activity of Synthetic Peptides 678 9. Revisiting Hydrogen-Bonded Rings and Polypeptide Helices 678

Structural chemistry of peptides containing backbone expanded amino acid residues: conformational features of β, γ, and hybrid peptides.

3210-3213 The specific incorporation per C4 unit, 3.3%, calculated from 13C NMR data (Table I), is identical with that obtained from I4C radioactivity measurements. The signals due to the I3C-enriched carbon atoms in the proton decoupled I3C NMR spectrum of labeled retronecine appear as multiplets (Table

Padmanabhan Balaram

Papers

Structural characteristics of .alpha.-helical peptide molecules containing Aib residues

Design of folded peptides.

The stereochemistry of peptides containing alpha-aminoisobutyric acid.

Structural chemistry of peptides containing backbone expanded amino acid residues: conformational features of β, γ, and hybrid peptides.

Asymmetric Total Synthesis of Erythromycin. 1. Synthesis of an Erythronolide A Seco Acid Derivative via Asymmetric Induction