Enhanced fold recognition using efficient short fragment clustering

The main structure aligner in the CCP4 Software Suite, SSM (Secondary Structure Matching) has a limited applicability on the intermediate stages of the structure solution process, when the secondary structure cannot be reliably computed due to structural incompleteness or a fragmented mainchain. In this study, we describe a new algorithm for the alignment and comparison of protein structures in CCP4, which was designed to overcome SSM's limitations but retain its quality and speed. The new algorithm, named GESAMT (General Efficient Structural Alignment of Macromolecular Targets), employs the old idea of deriving the global structure similarity from a promising set of locally similar short fragments, but uses a few technical solutions that make it considerably faster. A comparative sensitivity and selectivity analysis revealed an unexpected significant improvement in the fold recognition properties of the new algorithm, which also makes it useful for applications in the structural bioinformatics domain. The new tool is included in the CCP4 Software Suite starting from version 6.3

Structures of Phytophthora RXLR Effector Proteins: a conserved but adaptable fold underpins functional diversity

Phytopathogens deliver effector proteins inside host plant cells to promote infection. These proteins can also be sensed by the plant immune system, leading to restriction of pathogen growth. Effector genes can display signatures of positive selection and rapid evolution, presumably a consequence of their co-evolutionary arms race with plants. The molecular mechanisms underlying how effectors evolve to gain new virulence functions and/or evade the plant immune system are poorly understood. Here, we report the crystal structures of the effector domains from two oomycete RXLR proteins, Phytophthora capsici AVR3a11 and Phytophthora infestans PexRD2. Despite sharin

CCP4 Software Suite: historia, evolución, contenido, retos y perspectivas de futuro

Collaborative Computational Project Number 4 (CCP4) in Protein Crystallography is a public resource for producing and supporting a world-leading, integrated Suite of programs that allows researchers to determine macromolecular structures by X-ray crystallography, and other biophysical techniques. CCP4 supports the widest possible researcher community, embracing academic, not for profit, and for profit research. The primary aims of CCP4 include development and support of the development of cutting edge approaches to experimental determination and analysis of protein structure, with integration of them into the suite for worldwide dissemination. In addition, CCP4 plays an important role in the education and training of scientists in experimental structural biology. In this paper, we overview CCP4’s 35-year long history and (technical) milestones of its evolution. We will also consider how a particular structure of CCP4 Suite and Collaboration has emerged, its main functionality, current state and plans for future.“Collaborative Computational Project Number 4 (CCP4)” en Cristalografía de Proteínas es un recurso público líder mundial, encaminado a producir y mantener un conjunto integrado de programas que permite a los investigadores determinar estructuras macromoleculares mediante cristalografía de rayos-X, así como por otras técnicas biofísicas. CCP4 va dirigido a la más amplia comunidad científica posible, abarcando investigaciones en el ámbito académico, tanto sin ánimo de lucro como con él. Sus objetivos principales incluyen el desarrollo y soporte de metodologías punteras para la determinación y análisis de estructuras de proteínas, integradas en un conjunto bien definido para facilitar su fácil difusión mundial. Además, CCP4 juega un papel importante en la formación y entrenamiento de científicos en biología estructural experimental. En este artículo, ofreceré una visión de conjunto de la larga historia e hitos técnicos de CCP4 (35 años) y consideraré cómo ha surgido la particular estructura colaborativa de CCP4, sus características más notables, estado actual y perspectivas futuras

Quantum mechanism of light transmission by the intermediate filaments in some specialized optically transparent cells

Some very transparent cells in the optical tract of vertebrates, such as the lens fiber cells, possess certain types of specialized intermediate filaments (IFs) that have essential significance for their transparency. The exact mechanism describing why the IFs are so important for transparency is unknown. Recently, transparency was described also in the retinal Muller cells (MCs). We report that the main processes of the MCs contain bundles of long specialized IFs, each about 10 nm in diameter; most likely, these filaments are the channels providing light transmission to the photoreceptor cells in mammalian and avian retinas. We interpret the transmission of light in such channels using the notions of quantum confinement, describing energy transport in structures with electroconductive walls and diameter much smaller than the wavelength of the respective photons. Model calculations produce photon transmission efficiency in such channels exceeding 0.8, in optimized geometry. We infer that protein molecules make up the channels, proposing a qualitative mechanism of light transmission by such structures. The developed model may be used to describe light transmission by the IFs in any transparent cells. (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE)PR NASA EPSCoR (NASA) [NNX13AB22A]; NIH [G12 MD007583]; Russian Science Foundation [16-14-10159]info:eu-repo/semantics/publishedVersio

Melting and evaporation transitions in small Al clusters: canonical Monte-Carlo simulations

A dimer of bound atoms cannot melt, only dissociate. Bulk metals show a well defined first order transition between their solid and liquid phases. The appearance of the melting transition is explored for increasing clusters sizes via the signatures in the specific heat and the root mean square of the bond lengths $\delta_{\rm B}$ (Berry parameter) by means of Monte-Carlo simulations of Al clusters modelled by Gupta potentials. Clear signatures of a melting transition appear for $N\sim 6$ atoms. Closed-shell effects are shown for clusters with up to 56 atoms. The melting transition is compared in detail with the dissociation transition, which induces a second and possibly much larger local maximum in the specific heat at higher temperatures. Larger clusters are shown to fragment into dimers and trimers, which in turn dissociate at higher temperatures.Comment: 6 pages, 7 figure

Crystal structure of the Legionella pneumophila Lpg2936 in complex with the cofactor S-adenosyl-L-methionine reveals novel insights into the mechanism of RsmE family methyltransferases

The methylationlation of U1498 located in the 16S ribosomal RNA of Escherichia coli is an important modification affecting ribosomal activity. RsmE methyltransferases methylate specifically this position in a mechanism that requires an S-adenosyl-L-methionine (AdoMet) molecule as cofactor. Here we report the structure of Apo and AdoMet-bound Lpg2936 from Legionella pneumophila at 1.5 Å and 2.3 Å, respectively. The protein comprises an N-terminal PUA domain and a C-terminal SPOUT domain. The latter is responsible for protein dimerization and cofactor binding. Comparison with similar structures suggests that Lpg2936 is an RsmE-like enzyme that can target the equivalent of U1498 in the L. pneumophila ribosomal RNA, thereby potentially enhancing ribosomal activity during infection-mediated effector production. The multiple copies of the enzyme found in both structures reveal a flexible conformation of the bound AdoMet ligand. Isothermal titration calorimetry measurements suggest an asymmetric two site binding mode. Our results therefore also provide unprecedented insights into AdoMet/RsmE interaction, furthering our understanding of the RsmE catalytic mechanism. This article is protected by copyright. All rights reserved

Recent developments in MrBUMP : better search-model preparation, graphical interaction with search models, and solution improvement and assessment

Increasing sophistication in molecular-replacement (MR) software and the rapid expansion of the PDB in recent years have allowed the technique to become the dominant method for determining the phases of a target structure in macromolecular X-ray crystallography. In addition, improvements in bioinformatic techniques for finding suitable homologous structures for use as MR search models, combined with developments in refinement and model-building techniques, have pushed the applicability of MR to lower sequence identities and made weak MR solutions more amenable to refinement and improvement. MrBUMP is a CCP4 pipeline which automates all stages of the MR procedure. Its scope covers everything from the sourcing and preparation of suitable search models right through to rebuilding of the positioned search model. Recent improvements to the pipeline include the adoption of more sensitive bioinformatic tools for sourcing search models, enhanced model-preparation techniques including better ensembling of homologues, and the use of phase improvement and model building on the resulting solution. The pipeline has also been deployed as an online service through CCP4 online, which allows its users to exploit large bioinformatic databases and coarse-grained parallelism to speed up the determination of a possible solution. Finally, the molecular-graphics application CCP4mg has been combined with MrBUMP to provide an interactive visual aid to the user during the process of selecting and manipulating search models for use in MR. Here, these developments in MrBUMP are described with a case study to explore how some of the enhancements to the pipeline and to CCP4mg can help to solve a difficult case

An ultralong CDRH2 in HCV neutralizing antibody demonstrates structural plasticity of antibodies against E2 glycoprotein

A vaccine protective against diverse HCV variants is needed to control the HCV epidemic. Structures of E2 complexes with front layer-specific broadly neutralizing antibodies (bNAbs) isolated from HCV-infected individuals, revealed a disulfide bond-containing CDRH3 that adopts straight (individuals who clear infection) or bent (individuals with chronic infection) conformation. To investigate whether a straight versus bent disulfide bond-containing CDRH3 is specific to particular HCV-infected individuals, we solved a crystal structure of the HCV E2 ectodomain in complex with AR3X, a bNAb with an unusually long CDRH2 that was isolated from the chronically-infected individual from whom the bent CDRH3 bNAbs were derived. The structure revealed that AR3X utilizes both its ultralong CDRH2 and a disulfide motif-containing straight CDRH3 to recognize the E2 front layer. These results demonstrate that both the straight and bent CDRH3 classes of HCV bNAb can be elicited in a single individual, revealing a structural plasticity of VH1-69-derived bNAbs

Electronic and magnetic properties of multishell Co nanowires coated with Cu

The structural, electronic, and magnetic properties of ultrathin Cu-coated Co nanowires have been studied by using empirical genetic algorithm simulations and a tight-binding $spd$ model Hamiltonian in the unrestricted Hartree-Hock approximation. For some specific stoichiometric compositions, Cu atoms occupy the surface, while Co atoms prefer to stay in the interior, forming the perfect coated multishell structures. The outer Cu layers lead to substantial variations of the magnetic moment of interior Co atoms, depending on the structure and thickness of Cu layers. In particular, single Co atom row in the center of nanowire is found to be nonmagnetic when coated with two Cu layers. All the other Co nanowires in the coated Cu shell are still magnetic but the magnetic moments are reduced as compared with Co nanowires without Cu coating. The interaction between Cu and Co atoms induces nonzero magnetic moment for Cu atoms.Comment: 7 pages, 2 fugure