Functional activity of the H3.3 histone chaperone complex HIRA requires trimerization of the HIRA subunit.

The HIRA histone chaperone complex deposits the histone variant H3.3 onto chromatin in a DNA synthesis-independent manner. It comprises three identified subunits, HIRA, UBN1 and CABIN1, however the functional oligomerization state of the complex has not been investigated.

Development of a Nanobody-based lateral flow assay to detect active Trypanosoma congolense infections.

Animal African trypanosomosis (AAT), a disease affecting livestock, is caused by parasites of the Trypanosoma genus (mainly T. vivax and T. congolense).

Correction: Experimental African trypanosome infection suppresses the development of multiple myeloma in mice by inducing intrinsic apoptosis of malignant plasma cells.

[This corrects the article DOI: 10.18632/oncotarget.18152.

Molecular Motions and Interactions in Aqueous Solutions of Thymosin-β , Stabilin C-Terminal Domain (CTD) and Their 1:1 Complex Studied by H NMR Spectroscopy.

Wide-line H NMR measurements were extended and all results were reinterpreted in a new thermodynamics-based approach to study aqueous solutions of thymosin-β (Tβ ), stabilin C-terminal domain (CTD) and their 1:1 complex. The energy distributions of the potential barriers, which control motion of protein-bound water molecules, were determined. Heterogeneous and homogeneous regions were found at the protein-water interface.

Experimental African trypanosome infection suppresses the development of multiple myeloma in mice by inducing intrinsic apoptosis of malignant plasma cells.

Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells in the bone marrow (BM). Recently, several studies have highlighted the role of pathogens in either promoting or dampening malignancies of unrelated origin. is an extracellular protozoan parasite which causes sleeping sickness.

H, N, C resonance assignment of plant dehydrin early response to dehydration 10 (ERD10).

Early response to dehydration 10 protein (ERD10) is an intrinsically disordered protein from Arabidopsis thaliana. The protein is upregulated during stress however its mechanism of action at atomic level is not well understood. In the present work multidimensional NMR methodologies are used in order to facilitate the process of chemical shift assignment.

Hydrogen Mobility and Protein-Water Interactions in Proteins in the Solid State.

In this work the groundwork is laid for characterizing the mobility of hydrogen-hydrogen pairs (proton-proton radial vectors) in proteins in the solid state that contain only residual water. In this novel approach, we introduce new ways of analyzing and interpreting data: 1) by representing hydrogen mobility (HM) and melting diagram (MD) data recorded by wide-line H NMR spectroscopic analysis as a function of fundamental temperature (thermal excitation energy); 2) by suggesting a novel mode of interpretation of these parameters that sheds light on details of protein-water interactions, such as the exact amount of water molecules and the distribution of barrier potentials pertaining to their rotational and surface translational mobility; 3) by relying on directly determined physical observables. We illustrate the power of this approach by studying the behavior of two proteins, the structured enzyme lysozyme and the intrinsically disordered ERD14.

DisProt 7.0: a major update of the database of disordered proteins.

The Database of Protein Disorder (DisProt, URL: www.disprot.org) has been significantly updated and upgraded since its last major renewal in 2007.

A monoclonal antibody-based immunoassay to measure the antibody response against the repeat region of the circumsporozoite protein of Plasmodium falciparum.

Background: The malaria vaccine candidate RTS,S/AS01 (GSK Vaccines) induces high IgG concentration against the circumsporozoite protein (CSP) of Plasmodium falciparum. In human vaccine recipients circulating anti-CSP antibody concentrations are associated with protection against infection but appear not to be the correlate of protection. However, in a humanized mouse model of malaria infection prophylactic administration of a human monoclonal antibody (MAL1C), derived from a RTS,S/AS01-immunized volunteer, directed against the CSP repeat region, conveyed full protection in a dose-dependent manner suggesting that antibodies alone are able to prevent P.

Investigating the Molecular Mechanisms Behind Uncharacterized Cysteine Losses from Prediction of Their Oxidation State.

Cysteines are among the rarest amino acids in nature, and are both functionally and structurally very important for proteins. The ability of cysteines to form disulfide bonds is especially relevant, both for constraining the folded state of the protein and for performing enzymatic duties. But how does the variation record of human proteins reflect their functional importance and structural role, especially with regard to deleterious mutations? We created HUMCYS, a manually curated dataset of single amino acid variants that (1) have a known disease/neutral phenotypic outcome and (2) cause the loss of a cysteine, in order to investigate how mutated cysteines relate to structural aspects such as surface accessibility and cysteine oxidation state.

Essential functions linked with structural disorder in organisms of minimal genome.

Unlabelled: Intrinsically disordered regions (IDRs) of proteins fulfill important regulatory roles in most organisms. However, the proteins of certain endosymbiont and intracellular pathogenic bacteria with extremely reduced genomes contain disproportionately small amounts of IDRs, consisting almost entirely of folded domains. As their genomes co-evolving with their hosts have been reduced in unrelated lineages, the proteomes of these bacteria represent independently evolved minimal protein sets.

The Dermis as a Delivery Site of Trypanosoma brucei for Tsetse Flies.

Tsetse flies are the sole vectors of Trypanosoma brucei parasites that cause sleeping sickness. Our knowledge on the early interface between the infective metacyclic forms and the mammalian host skin is currently highly limited. Glossina morsitans flies infected with fluorescently tagged T.

Comparative evaluation of the nested ITS PCR against the 18S PCR-RFLP in a survey of bovine trypanosomiasis in Kwale County, Kenya.

We compared the nested internal transcribed spacer (ITS) PCR and the 18S PCR-RFLP (restriction-fragment length polymorphism) pan-trypanosome assays in a cross-sectional survey of bovine trypanosomiasis in 358 cattle in Kwale County, Kenya. The prevalence of trypanosomiasis as determined by the nested ITS PCR was 19.6% (70/358) and by 18S PCR-RFLP was 16.

Intrinsic protein disorder in histone lysine methylation.

Unlabelled: Histone lysine methyltransferases (HKMTs), catalyze mono-, di- and trimethylation of lysine residues, resulting in a regulatory pattern that controls gene expression. Their involvement in many different cellular processes and diseases makes HKMTs an intensively studied protein group, but scientific interest so far has been concentrated mostly on their catalytic domains. In this work we set out to analyze the structural heterogeneity of human HKMTs and found that many contain long intrinsically disordered regions (IDRs) that are conserved through vertebrate species.

The principle of conformational signaling.

Signal transduction is the primary process by which cells respond to changes in their physical and chemical environments. Cellular response is initiated through a signaling protein (a receptor), which interacts with the "signal", most often a novel molecule outside or inside the cell. The mechanism of activation of the receptor is a conformational change and/or covalent modification, which then sets in motion a signaling pathway, i.

Three reasons protein disorder analysis makes more sense in the light of collagen.

We have identified that the collagen helix has the potential to be disruptive to analyses of intrinsically disordered proteins. The collagen helix is an extended fibrous structure that is both promiscuous and repetitive. Whilst its sequence is predicted to be disordered, this type of protein structure is not typically considered as intrinsic disorder.

Design Principles Involving Protein Disorder Facilitate Specific Substrate Selection and Degradation by the Ubiquitin-Proteasome System.

The ubiquitin-proteasome system (UPS) regulates diverse cellular pathways by the timely removal (or processing) of proteins. Here we review the role of structural disorder and conformational flexibility in the different aspects of degradation. First, we discuss post-translational modifications within disordered regions that regulate E3 ligase localization, conformation, and enzymatic activity, and also the role of flexible linkers in mediating ubiquitin transfer and reaction processivity.

Tripartite degrons confer diversity and specificity on regulated protein degradation in the ubiquitin-proteasome system.

Specific signals (degrons) regulate protein turnover mediated by the ubiquitin-proteasome system. Here we systematically analyse known degrons and propose a tripartite model comprising the following: (1) a primary degron (peptide motif) that specifies substrate recognition by cognate E3 ubiquitin ligases, (2) secondary site(s) comprising a single or multiple neighbouring ubiquitinated lysine(s) and (3) a structurally disordered segment that initiates substrate unfolding at the 26S proteasome. Primary degron sequences are conserved among orthologues and occur in structurally disordered regions that undergo E3-induced folding-on-binding.

Redefining the BH3 Death Domain as a 'Short Linear Motif'.

B cell lymphoma-2 (BCL-2)-related proteins control programmed cell death through a complex network of protein-protein interactions mediated by BCL-2 homology 3 (BH3) domains. Given their roles as dynamic linchpins, the discovery of novel BH3-containing proteins has attracted considerable attention. However, without a clearly defined BH3 signature sequence the BCL-2 family has expanded to include a nebulous group of nonhomologous BH3-only proteins, now justified by an intriguing twist.

Functional Advantages of Conserved Intrinsic Disorder in RNA-Binding Proteins.

Proteins form large macromolecular assemblies with RNA that govern essential molecular processes. RNA-binding proteins have often been associated with conformational flexibility, yet the extent and functional implications of their intrinsic disorder have never been fully assessed. Here, through large-scale analysis of comprehensive protein sequence and structure datasets we demonstrate the prevalence of intrinsic structural disorder in RNA-binding proteins and domains.

SnapShot: Intrinsic Structural Disorder.

Many proteins (intrinsically disordered proteins, IDPs) or regions of proteins (intrinsically disordered regions, IDRs) lack a well-defined 3D structure under physiological conditions. Albeit unfolded and highly dynamic, these proteins are not denatured; rather, intrinsic structural disorder is their native, functional state.

DisCons: a novel tool to quantify and classify evolutionary conservation of intrinsic protein disorder.

Background: Analyzing the amino acid sequence of an intrinsically disordered protein (IDP) in an evolutionary context can yield novel insights on the functional role of disordered regions and sequence element(s). However, in the case of many IDPs, the lack of evolutionary conservation of the primary sequence can hamper the study of functionality, because the conservation of their disorder profile and ensuing function(s) may not appear in a traditional analysis of the evolutionary history of the protein.

Results: Here we present DisCons (Disorder Conservation), a novel pipelined tool that combines the quantification of sequence- and disorder conservation to classify disordered residue positions.

Production, purification and crystallization of a trans-sialidase from Trypanosoma vivax.

Sialidases and trans-sialidases play important roles in the life cycles of various microorganisms. These enzymes can serve nutritional purposes, act as virulence factors or mediate cellular interactions (cell evasion and invasion). In the case of the protozoan parasite Trypanosoma vivax, trans-sialidase activity has been suggested to be involved in infection-associated anaemia, which is the major pathology in the disease nagana.