PROFcon: novel prediction of long-range contacts

MOTIVATION: Despite the continuing advance in the experimental determination of protein structures, the gap between the number of known protein sequences and structures continues to increase. Prediction methods can bridge this sequence-structure gap only partially. Better predictions of non-local contacts between residues could improve comparative modeling, fold recognition and could assist in the experimental structure determination. RESULTS: Here, we introduced PROFcon, a novel contact prediction method that combines information from alignments, from predictions of secondary structure and solvent accessibility, from the region between two residues and from the average properties of the entire protein. In contrast to some other methods, PROFcon predicted short and long proteins at similar levels of accuracy. As expected, PROFcon was clearly less accurate when tested on sparse evolutionary profiles, that is, on families with few homologs. Prediction accuracy was highest for proteins belonging to the SCOP alpha/beta class. PROFcon compared favorably with state-of-the-art prediction methods at the CASP6 meeting. While the performance may still be perceived as low, our method clearly pushed the mark higher. Furthermore, predictions are already accurate enough to seed predictions of global features of protein structure.     

Solution structure of Archaeglobus fulgidis peptidyl-tRNA hydrolase (Pth2) provides evidence for an extensive conserved family of Pth2 enzymes in archea, bacteria, and eukaryotes

The solution structure of protein AF2095 from the thermophilic archaea Archaeglobus fulgidis, a 123-residue (13.6-kDa) protein, has been determined by NMR methods. The structure of AF2095 is comprised of four alpha-helices and a mixed beta-sheet consisting of four parallel and anti-parallel beta-strands, where the alpha-helices sandwich the beta-sheet. Sequence and structural comparison of AF2095 with proteins from Homo sapiens, Methanocaldococcus jannaschii, and Sulfolobus solfataricus reveals that AF2095 is a peptidyl-tRNA hydrolase (Pth2). This structural comparison also identifies putative catalytic residues and a tRNA interaction region for AF2095. The structure of AF2095 is also similar to the structure of protein TA0108 from archaea Thermoplasma acidophilum, which is deposited in the Protein Data Bank but not functionally annotated. The NMR structure of AF2095 has been further leveraged to obtain good-quality structural models for 55 other proteins. Although earlier studies have proposed that the Pth2 protein family is restricted to archeal and eukaryotic organisms, the similarity of the AF2095 structure to human Pth2, the conservation of key active-site residues, and the good quality of the resulting homology models demonstrate a large family of homologous Pth2 proteins that are conserved in eukaryotic, archaeal, and bacterial organisms, providing novel insights in the evolution of the Pth and Pth2 enzyme families.     

Claude Fortier: the great history of neuroendocrinology

The work of Claude Fortier is linked to the history of neuroendocrinology. Through him and his pioneer work in Montreal with Hans Selye, the < Man of stress >, and at Laval University in Quebec City in his own laboratory, where all researchers involved in the study of the hypothalamo-hypophysial adrenal axis have been through, it is the whole saga of the search for the neuropeptide CRH (corticotropin releasing factor), and the harsh fight for the Nobel distinction that can be related. Among Claude Fortier's scientific discoveries, the feedback mechanisms of glucocorticoid hormones on brain and pituitary function, the presence of both mineralo and glucocorticoid receptors in some brain structures, and the introduction of computer science in biomedical research, can be cited. The consequences of these discoveries are illustrated in the pathologies linked to stress (anxiety, depression, addiction). Claude Fortier was not only a great figure in biomedical science, honored by several distinctions, but also an important personality in the policy of research in which he played a prominent role in Quebec medical research and allowed it to rank among the best in the world.     

Ulysses - an application for the projection of molecular interactions across species

We developed Ulysses as a user-oriented system that uses a process called Interolog Analysis for the parallel analysis and display of protein interactions detected in various species. Ulysses was designed to perform such Interolog Analysis by the projection of model organism interaction data onto homologous human proteins, and thus serves as an accelerator for the analysis of uncharacterized human proteins. The relevance of projections was assessed and validated against published reference collections. All source code is freely available, and the Ulysses system can be accessed via a web interface .     

Molecular analysis of aerobic phenylacetate degradation in Azoarcus evansii

The Azoarcus evansii gene which codes for phenylacetate-CoA ligase, an enzyme involved in the aerobic degradation of phenylacetate, was isolated from a genomic library, using as the probe a fragment of the gene which encodes the isoenzyme that is induced under anaerobic conditions. By this means both the gene and its flanking sequences were recovered. The gene is homologous to the phenylacetate-CoA ligase genes of Pseudomonas putida U and Escherichia coli W. Induction by phenylacetate under aerobic growth conditions was demonstrated using lacZ fusions. Western analysis showed that phenylacetate-CoA ligase is involved in the degradation of the aromatic amino acid phenylalanine. Genes coding for the phenylacetate-CoA ligase and for the putative hydroxylating enzyme were expressed in E. coli. Detection of 2-hydroxyphenylacetate in the recombinant E. coli strain indicated hydroxylation of phenylacetyl-CoA. The gene pacL, which codes for the putative ring-opening enzyme was mutated to enable the isolation of intermediates in aerobic phenylacetic acid degradation, which were characterized by GC-MS and NMR analyses.     

Modular construction of the protoderm and peripheral root cap in the “open” root apical meristem ofTrifolium repens cv. Ladino

Summary Roots with open apical organization are defined by not having specific tiers of initial cells in the root apical meristem; those with closed apical organization have specific initial tiers to which all cell files can be traced. An example of the clear organization of closed roots is the development protocol of the root cap and protoderm. The key event in differentiating these tissues is the T-division, a periclinal division of the root cap/protoderm (RCP) initial that establishes a module. Each module comprises two packets, the protoderm and peripheral root cap. Consecutive T-divisions of the same RCP initial produce up to five modules on average in a lineage of cells in white clover (Trifolium repens cv. Ladino), with all lineages around the circumference of the root dividing in waves to form one module prior to the next. On average, clover has approximately 32 axial protoderm and peripheral root cap cells in each module, and 32 RCP lineages. The occurrence of RCP T-divisions in white clover, a root with open apical organization, and the subsequent modular construction of the root cap and protoderm, provides a link between open and closed roots and suggests a common developmental feature that most roots of seed plants may share independent of their root meristem organization type. The open apical organization of the white clover root varies from roots with closed apical organization in that the RCP initials occur in staggered positions instead of connected to discrete tiers, and the peripheral root cap and columella daughter cells form additional layers of cells. White clover also forms root hairs on all protoderm cells irrespective of their position relative to the underlying cortical cells.Abbreviations RAM root apical meristem - RCP root cap protoderm - prc peripheral root cap     

PREFACE

This highlight section of the Annals of Botany contains a collectionof articles that focus on the structure and function of rootsof flowering plants. Most of the papers presented are basedon talks given at a symposium on root structure and functionat the XVII International Botanical Congress, Vienna, Austria,July 2005. Many of the articles, briefly capsulated below, examinethe interactions between plants and the rhizosphere—thebelow-ground environment that immediately surrounds the root.The rhizosphere is far more complex physically, chemically andbiologically than the above-ground environment of the shootbecause (1) rapid, long-distance movement of energy or matteris limited through     

Fetal microchimerism in kidney biopsies of lupus nephritis patients may be associated with a beneficial effect

IntroductionMicrochimeric male fetal cells (MFCs) have been associated with systemic lupus erythematosus, and published studies have further correlated MFC with lupus nephritis (LN). In the present study, we evaluated the frequency of MFC in the renal tissue of patients with LN.MethodsTwenty-seven renal biopsies were evaluated: Fourteen were from women with clinical and laboratory findings of LN, and thirteen were from controls. Genomic DNA was extracted from kidney biopsies, and the male fetal DNA was quantified using real-time quantitative polymerase chain reactions for the detection of specific Y chromosome sequences.ResultsMFCs were detected in 9 (64%) of 14 of patients with LN, whereas no MFCs were found in the control group (P = 0.0006). No differences in pregnancy history were found between patients with LN and the control group. Significantly higher amounts of MFCs were found in patients with LN with serum creatinine ≤1.5 mg/dl. Furthermore, women with MFCs had significantly better renal function at the time of biopsy (P = 0.03). In contrast, patients with LN without MFCs presented with more severe forms of glomerulonephritis (World Health Organization class IV = 60% and class V = 40%).ConclusionsOur data indicate a high prevalence of MFCs in renal biopsy specimens from women with LN, suggesting a role for MFCs in the etiology of LN. The present report also provides some evidence that MFCs could have a beneficial effect in this disease.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0615-4) contains supplementary material, which is available to authorized users.     

Dipeptide interactions with Zn(II)–cyclen artificial model for molecular recognition

The Zn(II)–cyclen–dipeptide ternary systems (where cyclen is abbreviated as L and dipeptide is glycylglycine (HL¹) or glycyl‐(S)‐alanine (HL²)) were investigated by potentiometry applying both “out‐of‐cell” and direct titrations and by ¹H NMR spectroscopy. Especially, the ¹H NMR study was found to be very efficient to estimate speciation in the systems. The results obtained under full equilibria indicated two main species, [Zn(L)(HL^1,2)]²⁺ and [Zn(L)(L^1,2)]⁺, in both the systems. In the [Zn(L)(HL^1,2)]²⁺ complex, presence of carbonyl‐carboxylate chelate was confirmed, and in the [Zn(L)(L^1,2)]⁺ species, the peptide coordination is re‐organized to carbonyl‐amine chelate or only terminal amino group is coordinated. Equilibrium constants describing [Zn(L)]²⁺–dipeptide interaction are relatively low, log K = 3.4 for Gly‐Gly and 4.1 for Gly‐(S)‐Ala, respectively. Nevertheless, the values are slightly higher than stability constants for interaction of Zn(II) with the dipeptides (i.e. [Zn(L^1,2)]⁺ species) where a chelate formation is expected. It indicates that interaction between Zn(II) ion in [Zn(L)]²⁺ and the dipeptides should be supported by some additional interactions. Potentiometry carried out under non‐equilibrum condition showed different species where these additional stabilizing forces play more important role. Copyright © 2015 John Wiley & Sons, Ltd.