Protein Domain Boundary Predictions: A Structural Biology Perspective

One of the important fields to apply computational tools for domain boundaries prediction is structural biology. They can be used to design protein constructs that must be expressed in a stable and functional form and must produce diffraction-quality crystals. However, prediction of protein domain boundaries on the basis of amino acid sequences is still very problematical. In present study the performance of several computational approaches are compared. It is observed that the statistical significance of most of the predictions is rather poor. Nevertheless, when the right number of domains is correctly predicted, domain boundaries are predicted within very few residues from their real location. It can be concluded that prediction methods cannot be used yet as routine tools in structural biology, though some of them are rather promising

Origin of the Spin-Orbital Liquid State in a Nearly J=0 Iridate Ba3ZnIr2O9

We show using detailed magnetic and thermodynamic studies and theoretical calculations that the ground state of Ba3ZnIr2O9 is a realization of a novel spin-orbital liquid state. Our results reveal that Ba3ZnIr2O9 with Ir5+ (5d(4)) ions and strong spin-orbit coupling (SOC) arrives very close to the elusive J = 0 state but each Ir ion still possesses a weak moment. Ab initio density functional calculations indicate that this moment is developed due to superexchange, mediated by a strong intradimer hopping mechanism. While the Ir spins within the structural Ir2O9 dimer are expected to form a spin-orbit singlet state (SOS) with no resultant moment, substantial frustration arising from interdimer exchange interactions induce quantum fluctuations in these possible SOS states favoring a spin-orbital liquid phase down to at least 100 mK

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally diverse individuals (European, African, Asian, and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole-genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n = 109,122 individuals. We identified 59 sentinel variants (p < 5 × 10−9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated that the independent signals colocalized with cell-type-specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated that our TL polygenic trait scores (PTSs) were associated with an increased risk of cancer-related phenotypes

1H, 15N, 13C resonance assignment of the human CD44 cytoplasmic tail (669–742)

CD44 is a universally and abundantly expressed single-pass type I protein that spans the cytoplasmic membrane and is considered the principal receptor for hyaluronan in the extracellular matrix. CD44 exerts a multitude of biological functions, especially in cell adhesion and migration, and its deregulation has several pathological implications, including a putative role in cancer cell dissemination. Here we report the NMR chemical shift assignment of the recombinant intrinsically disordered CD44 cytoplasmic region (669–742).© The Author(s) 201

RNA-protein interactions in an unstructured context

Despite their importance, our understanding of noncovalent RNA–protein interactions is incomplete. This especially concerns the binding between RNA and unstructured protein regions, a widespread class of such interactions. Here, we review the recent experimental and computational work on RNA–protein interactions in an unstructured context with a particular focus on how such interactions may be shaped by the intrinsic interaction affinities between individual nucleobases and protein side chains. Specifically, we articulate the claim that the universal genetic code reflects the binding specificity between nucleobases and protein side chains and that, in turn, the code may be seen as the Rosetta stone for understanding RNA–protein interactions in general.© 2018 The Author

Structures Today and beyond 2000; papers presented at the international research jamboree

Publ. in association with American Society of Civil EngineersAvailable from British Library Document Supply Centre- DSC:q91/17695(Structures) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

mRNA/protein sequence complementarity and its determinants: The impact of affinity scales

It has recently been demonstrated that the nucleobase-density profiles of mRNA coding sequences are related in a complementary manner to the nucleobase-affinity profiles of their cognate protein sequences. Based on this, it has been proposed that cognate mRNA/protein pairs may bind in a co-aligned manner, especially if unstructured. Here, we study the dependence of mRNA/protein sequence complementarity on the properties of the nucleobase/amino-acid affinity scales used. Specifically, we sample the space of randomly generated scales by employing a Monte Carlo strategy with a fitness function that depends directly on the level of complementarity. For model organisms representing all three domains of life, we show that even short searches reproducibly converge upon highly optimized scales, implying that the topology of the underlying fitness landscape is decidedly funnel-like. Furthermore, the optimized scales, generated without any consideration of the physicochemical attributes of nucleobases or amino acids, resemble closely the nucleobase/amino-acid binding affinity scales obtained from experimental structures of RNA-protein complexes. This provides support for the claim that mRNA/protein sequence complementarity may indeed be related to binding between the two. Finally, we characterize suboptimal scales and show that intermediate-to-high complementarity can be reached by substantially diverse scales, but with select amino acids contributing disproportionally. Our results expose the dependence of cognate mRNA/protein sequence complementarity on the properties of the underlying nucleobase/amino-acid affinity scales and provide quantitative constraints that any physical scales need to satisfy for the complementarity to hold.© 2017 Bartonek, Zagrovi