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

The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

J. Appl. Cryst.の発刊に際して

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

Nature relies on large molecules to carry out sophisticated chemical operations, such as catalysis, tight and specific binding, directed flow of electrons, or controlled crystallization of inorganic phases. The polymers entrusted with these crucial tasks, mostly proteins but sometimes RNA, are unique relative to other biological and synthetic polymers in that they adopt specific compact conformations that are thermodynamically and kinetically stable. These folding patterns generate “active sites” via precise three-dimensional arrangement of functional groups. In terms of covalent connectivity, the groups that comprise the active site are often widely spaced along the polymer backbone. The remarkable range of chemical capabilities that evolution has elicited from proteins suggests that it might be possible to design analogous capabilities into unnatural polymers that fold into compact and specific conformations. Since biological evolution has operated under many constraints, the functional properties of proteins and RNA should be viewed as merely exemplifying the potential of compactly folded polymers. The chemist’s domain includes all possible combinations of the elements, and the biological realm, vast and complex though it may be, is only a small part of that domain. Therefore, realization of the potential of folding polymers may be limited more by the human imagination than by physical barriers. I use the term “foldamer” to describe any polymer with a strong tendency to adopt a specific compact conformation. Among proteins, the term “compact” is associated with tertiary structure, and there is as yet no synthetic polymer that displays a specific tertiary structure. Protein tertiary structure arises from the assembly of elements of regular secondary structure (helices, sheets, and turns). The first step in foldamer design must therefore be to identify new backbones with well-defined secondary structural preferences. “Well-defined” in this case means that the conformational preference should be displayed in solution by oligomers of modest length, and I will designate as a foldamer any oligomer that meets this criterion. Within the past decade, a handful of research groups have described unnatural oligomers with interesting conformational propensities. The motivations behind such efforts are varied, but these studies suggest a collective, emerging realization that control over oligomer and polymer folding could lead to new types of molecules with useful properties. The purpose of this “manifesto” is to introduce a large audience to the broad research horizons offered by the concept of synthetic foldamers. The path to creating useful foldamers involves several daunting steps. (i) One must identify new polymeric backbones with suitable folding propensities. This goal includes developing a predictively useful understanding of the relationship between the repetitive features of monomer structure and conformational properties at the polymer level. (ii) One must endow the resulting foldamers with interesting chemical functions, by design, by randomization and screening (“evolution”), or by some combination of these two approaches. (iii) For technological utility, one must be able to produce a foldamer efficiently, which will generally include preparation of the constituent monomers in stereochemically pure form and optimization of heteropolymer synthesis. Each of these steps involves fascinating chemical challenges; the first step is the focus of this Account.

Foldamers: A Manifesto

Predictions of protein conformational disorder are important in structural biology since they can allow the elimination of protein constructs, the three-dimensional structure of which cannot be determined since they are natively unfolded. Here a new procedure is presented that allows one to predict with high accuracy disordered residues on the basis of protein sequences. It makes use of twelve prediction methods and merges their results by using least-squares optimization. A statistical survey of the Protein Data Bank is also reported, in order to know how many residues can be disordered in proteins that were crystallized and the three-dimensional structure of which was determined.

/pdf/consensus-prediction-of-protein-conformational-disorder-from-2bos3genmb.pdf

Consensus prediction of protein conformational disorder from amino acidic sequence.

The known crystal structures of the o-benzoquinone monooxime complexes with d metals have been examined. In these compounds the ligands can, in principle, be present as o-benzoquinone monooximes I or o-nitrosophenols II. The available data indicate that the ligands are always intermediate between these limiting forms. Moreover, a comparison between the structures of the free ligands and those of their d-metal complexes shows that complexation to a d-metal influences the mesomeric equilibrium between forms I and II, causing a shift towards II. This feature is discussed in terms of the interaction of the ligands with the d orbitals of the metal.

Studies on metal complexes of ortho-quinone monooximes. Part 9. Analysis of the charge distribution within the o-quinone monooxime ligands through crystallographic data

Background
Hydration is crucial for RNA structure and function. X-ray crystallography is the most commonly used method to determine RNA structures and hydration and, therefore, statistical surveys are based on crystallographic results, the number of which is quickly increasing.

/pdf/hydration-sites-of-unpaired-rna-bases-a-statistical-analysis-kohjmokgx5.pdf

Hydration sites of unpaired RNA bases: a statistical analysis of the PDB structures

The highly conserved G-M-N motif of the CorA-Mrs2-Alr1 family of Mg2+ channels has been shown to be essential for Mg2+ transport. We performed random mutagenesis of the G-M-N sequence of Saccharomyces cerevisiae Mrs2p in an unbiased genetic screen. A large number of mutants still capable of Mg2+ influx, albeit below the wild-type level, were generated. Growth complementation assays, performed in media supplemented with Ca2+ or Co2+ or Mn2+ or Zn2+ at varying concentrations, lead to identification of mutants with reduced growth in the presence of Mn2+ and Zn2+. We hereby conclude that (1) at least two, but predominantly all three amino acids of the G-M-N motif must be replaced by certain combinations of other amino acids to remain functional, (2) replacement of any single amino acid within the G-M-N motif always impairs the function of Mrs2p, and (3) we show that the G-M-N motif determines ion selectivity, likely in concurrence with the negatively charged loop at the entrance of the channel thereby forming the Mrs2p selectivity filter.

/pdf/the-g-m-n-motif-determines-ion-selectivity-in-the-yeast-40029ripfx.pdf

Oliviero Carugo

Papers

Consensus prediction of protein conformational disorder from amino acidic sequence.

Studies on metal complexes of ortho-quinone monooximes. Part 9. Analysis of the charge distribution within the o-quinone monooxime ligands through crystallographic data

Hydration sites of unpaired RNA bases: a statistical analysis of the PDB structures

The G-M-N motif determines ion selectivity in the yeast magnesium channel Mrs2p

A conformational study of N-tosyl oxazolidines using molecular mechanics and crystallography