scholarly journals Superimposition of Viral Protein Structures: A Means to Decipher the Phylogenies of Viruses

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1146
Author(s):  
Janne J. Ravantti ◽  
Ane Martinez-Castillo ◽  
Nicola G.A. Abrescia
Keyword(s):  
Protein Function ◽  
Major Capsid Protein ◽  
Sequence Similarity ◽  
Protein Structures ◽  
Structural Homology ◽  
Structural Comparison ◽  
Emerging Viruses ◽  
Enveloped Viruses ◽  
Original Observation ◽  
Jelly Roll

Superimposition of protein structures is key in unravelling structural homology across proteins whose sequence similarity is lost. Structural comparison provides insights into protein function and evolution. Here, we review some of the original findings and thoughts that have led to the current established structure-based phylogeny of viruses: starting from the original observation that the major capsid proteins of plant and animal viruses possess similar folds, to the idea that each virus has an innate “self”. This latter idea fueled the conceptualization of the PRD1-adenovirus lineage whose members possess a major capsid protein (innate “self”) with a double jelly roll fold. Based on this approach, long-range viral evolutionary relationships can be detected allowing the virosphere to be classified in four structure-based lineages. However, this process is not without its challenges or limitations. As an example of these hurdles, we finally touch on the difficulty of establishing structural “self” traits for enveloped viruses showcasing the coronaviruses but also the power of structure-based analysis in the understanding of emerging viruses

scholarly journals Including Functional Annotations and Extending the Collection of Structural Classifications of Protein Loops (ArchDB)

2007 ◽  
Vol 1 ◽  
pp. 117793220700100 ◽  
Author(s):  
Antoni Hermoso ◽  
Jordi Espadaler ◽  
E Enrique Querol ◽  
Francesc X. Aviles ◽  
Michael J.E. Sternberg ◽  
...  
Keyword(s):  
Protein Function ◽  
Structure Prediction ◽  
Sequence Similarity ◽  
Protein Structures ◽  
Fold Increase ◽  
Loop Structure ◽  
Biological Databases ◽  
Loop Modeling ◽  
And Function

Loops represent an important part of protein structures. The study of loop is critical for two main reasons: First, loops are often involved in protein function, stability and folding. Second, despite improvements in experimental and computational structure prediction methods, modeling the conformation of loops remains problematic. Here, we present a structural classification of loops, ArchDB, a mine of information with application in both mentioned fields: loop structure prediction and function prediction. ArchDB ( http://sbi.imim.es/archdb ) is a database of classified protein loop motifs. The current database provides four different classification sets tailored for different purposes. ArchDB-40, a loop classification derived from SCOP40, well suited for modeling common loop motifs. Since features relevant to loop structure or function can be more easily determined on well-populated clusters, we have developed ArchDB-95, a loop classification derived from SCOP95. This new classification set shows a ~40% increase in the number of subclasses, and a large 7-fold increase in the number of putative structure/function-related subclasses. We also present ArchDB-EC, a classification of loop motifs from enzymes, and ArchDB-KI, a manually annotated classification of loop motifs from kinases. Information about ligand contacts and PDB sites has been included in all classification sets. Improvements in our classification scheme are described, as well as several new database features, such as the ability to query by conserved annotations, sequence similarity, or uploading 3D coordinates of a protein. The lengths of classified loops range between 0 and 36 residues long. ArchDB offers an exhaustive sampling of loop structures. Functional information about loops and links with related biological databases are also provided. All this information and the possibility to browse/query the database through a web-server outline an useful tool with application in the comparative study of loops, the analysis of loops involved in protein function and to obtain templates for loop modeling.

scholarly journals Structure Unveils Relationships between RNA Virus Polymerases

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 313
Author(s):  
Heli A. M. Mönttinen ◽  
Janne J. Ravantti ◽  
Minna M. Poranen
Keyword(s):  
Phylogenetic Tree ◽  
Rna Viruses ◽  
Rna Virus ◽  
Sequence Similarity ◽  
Protein Structures ◽  
Structural Similarity ◽  
Functional Differentiation ◽  
Comparison Method ◽  
Homologous Structure ◽  
Biological Entities

RNA viruses are the fastest evolving known biological entities. Consequently, the sequence similarity between homologous viral proteins disappears quickly, limiting the usability of traditional sequence-based phylogenetic methods in the reconstruction of relationships and evolutionary history among RNA viruses. Protein structures, however, typically evolve more slowly than sequences, and structural similarity can still be evident, when no sequence similarity can be detected. Here, we used an automated structural comparison method, homologous structure finder, for comprehensive comparisons of viral RNA-dependent RNA polymerases (RdRps). We identified a common structural core of 231 residues for all the structurally characterized viral RdRps, covering segmented and non-segmented negative-sense, positive-sense, and double-stranded RNA viruses infecting both prokaryotic and eukaryotic hosts. The grouping and branching of the viral RdRps in the structure-based phylogenetic tree follow their functional differentiation. The RdRps using protein primer, RNA primer, or self-priming mechanisms have evolved independently of each other, and the RdRps cluster into two large branches based on the used transcription mechanism. The structure-based distance tree presented here follows the recently established RdRp-based RNA virus classification at genus, subfamily, family, order, class and subphylum ranks. However, the topology of our phylogenetic tree suggests an alternative phylum level organization.

scholarly journals Electron Cryotomography of Tula Hantavirus Suggests a Unique Assembly Paradigm for Enveloped Viruses

2010 ◽  
Vol 84 (10) ◽  
pp. 4889-4897 ◽  
Author(s):  
Juha T. Huiskonen ◽  
Jussi Hepojoki ◽  
Pasi Laurinmäki ◽  
Antti Vaheri ◽  
Hilkka Lankinen ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Hemorrhagic Fever ◽  
Membrane Curvature ◽  
Emerging Viruses ◽  
Enveloped Viruses ◽  
Viral Membrane ◽  
Density Maps ◽  
Virion Structure ◽  
Electron Cryotomography ◽  
Assembly Principles

ABSTRACT Hantaviruses (family Bunyaviridae) are rodent-borne emerging viruses that cause a serious, worldwide threat to human health. Hantavirus diseases include hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. Virions are enveloped and contain a tripartite single-stranded negative-sense RNA genome. Two types of glycoproteins, GN and GC, are embedded in the viral membrane and form protrusions, or “spikes.” The membrane encloses a ribonucleoprotein core, which consists of the RNA segments, the nucleocapsid protein, and the RNA-dependent RNA polymerase. Detailed information on hantavirus virion structure and glycoprotein spike composition is scarce. Here, we have studied the structures of Tula hantavirus virions using electron cryomicroscopy and tomography. Three-dimensional density maps show how the hantavirus surface glycoproteins, membrane, and ribonucleoprotein are organized. The structure of the GN-GC spike complex was solved to 3.6-nm resolution by averaging tomographic subvolumes. Each spike complex is a square-shaped assembly with 4-fold symmetry. Spike complexes formed ordered patches on the viral membrane by means of specific lateral interactions. These interactions may be sufficient for creating membrane curvature during virus budding. In conclusion, the structure and assembly principles of Tula hantavirus exemplify a unique assembly paradigm for enveloped viruses.

T26248G-transversion mutation in exon7 of the putative methyltransferase Nsun7 gene causes a change in protein folding associated with reduced sperm motility in asthenospermic men

2015 ◽  
Vol 27 (3) ◽  
pp. 471 ◽  
Author(s):  
Nahid Khosronezhad ◽  
Abasalt Hosseinzadeh Colagar ◽  
Syed Golam Ali Jorsarayi
Keyword(s):  
Protein Folding ◽  
Sperm Motility ◽  
Protein Function ◽  
Direct Sequencing ◽  
Protein Structures ◽  
Single Strand Conformation Polymorphism ◽  
Extraction Methods ◽  
World Health ◽  
Transversion Mutation ◽  
Health Organization

The NOP2/Sun domain family, member 7 (Nsun7) gene, which encodes putative methyltransferase Nsun7, has a role in sperm motility in mice. In humans, this gene is located on chromosome 4 with 12 exons. The aim of the present study was to investigate mutations of exon 7 in the normospermic and asthenospermic men. Semen samples were collected from the Fatemezahra IVF centre (Babol, Iran) and analysed on the basis of World Health Organization (WHO) guidelines using general phenol–chloroform DNA extraction methods. Exon 7 was amplified using Sun7-F and Sun7-R primers. Bands on samples from asthenospermic men that exhibited different patterns of movement on single-strand conformation polymorphism gels compared with normal samples were identified and subjected to sequencing for further identification of possible mutations. Direct sequencing of polymerase chain reaction (PCR) products, along with their analysis, confirmed C26232T-transition and T26248G-transversion mutations in asthenospermic men. Comparison of normal and mutant protein structures of Nsun7 indicated that the amino acid serine was converted to alanine, the structure of the helix, coil and strand was changed, and the protein folding and ligand binding sites were changed in samples from asthenospermic men with a transversion mutation in exon 7, indicating impairment of protein function. Because Nsun7 gene products have a role in sperm motility, if an impairment occurs in exon 7 of this gene, it may lead to infertility. The transversion mutation in exon 7 of the Nsun7 gene can be used as an infertility marker in asthenospermic men.

scholarly journals On the Importance of Atomic Fluctuations, Protein Flexibility, and Solvent in Ion Permeation

2004 ◽  
Vol 124 (6) ◽  
pp. 679-690 ◽  
Author(s):  
Toby W. Allen ◽  
O.S. Andersen ◽  
Benoit Roux
Keyword(s):  
Ion Channel ◽  
Protein Function ◽  
Channel Model ◽  
Protein Structures ◽  
Thermal Fluctuations ◽  
Model Parameters ◽  
Ion Permeation ◽  
Model Calculations ◽  
Channel Interactions ◽  
Solvent Molecules

Proteins, including ion channels, often are described in terms of some average structure and pictured as rigid entities immersed in a featureless solvent continuum. This simplified view, which provides for a convenient representation of the protein's overall structure, incurs the risk of deemphasizing important features underlying protein function, such as thermal fluctuations in the atom positions and the discreteness of the solvent molecules. These factors become particularly important in the case of ion movement through narrow pores, where the magnitude of the thermal fluctuations may be comparable to the ion pore atom separations, such that the strength of the ion channel interactions may vary dramatically as a function of the instantaneous configuration of the ion and the surrounding protein and pore water. Descriptions of ion permeation through narrow pores, which employ static protein structures and a macroscopic continuum dielectric solvent, thus face fundamental difficulties. We illustrate this using simple model calculations based on the gramicidin A and KcsA potassium channels, which show that thermal atomic fluctuations lead to energy profiles that vary by tens of kcal/mol. Consequently, within the framework of a rigid pore model, ion-channel energetics is extremely sensitive to the choice of experimental structure and how the space-dependent dielectric constant is assigned. Given these observations, the significance of any description based on a rigid structure appears limited. Creating a conducting channel model from one single structure requires substantial and arbitrary engineering of the model parameters, making it difficult for such approaches to contribute to our understanding of ion permeation at a microscopic level.

scholarly journals The proteome: structure, function and evolution

2006 ◽  
Vol 361 (1467) ◽  
pp. 441-451 ◽  
Author(s):  
Keiran Fleming ◽  
Lawrence A Kelley ◽  
Suhail A Islam ◽  
Robert M MacCallum ◽  
Arne Muller ◽  
...  
Keyword(s):  
Protein Function ◽  
Sequence Similarity ◽  
Structural Annotation ◽  
New Approach ◽  
Link Type ◽  
University College London ◽  
Automated Pipeline ◽  
3D Genomics ◽  
And Function ◽  
Structural Homologue

This paper reports two studies to model the inter-relationships between protein sequence, structure and function. First, an automated pipeline to provide a structural annotation of proteomes in the major genomes is described. The results are stored in a database at Imperial College, London (3D-GENOMICS) that can be accessed at www.sbg.bio.ic.ac.uk . Analysis of the assignments to structural superfamilies provides evolutionary insights. 3D-GENOMICS is being integrated with related proteome annotation data at University College London and the European Bioinformatics Institute in a project known as e-protein ( http://www.e-protein.org/ ). The second topic is motivated by the developments in structural genomics projects in which the structure of a protein is determined prior to knowledge of its function. We have developed a new approach PHUNCTIONER that uses the gene ontology (GO) classification to supervise the extraction of the sequence signal responsible for protein function from a structure-based sequence alignment. Using GO we can obtain profiles for a range of specificities described in the ontology. In the region of low sequence similarity (around 15%), our method is more accurate than assignment from the closest structural homologue. The method is also able to identify the specific residues associated with the function of the protein family.

scholarly journals Crystal structure of the N-terminal domain of VqsR fromPseudomonas aeruginosaat 2.1 Å resolution

2017 ◽  
Vol 73 (7) ◽  
pp. 431-436
Author(s):  
Qing He ◽  
Kang Wang ◽  
Tiantian Su ◽  
Feng Wang ◽  
Lichuan Gu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Sequence Similarity ◽  
Transcriptional Regulator ◽  
Binding Domain ◽  
Structural Comparison ◽  
Homoserine Lactones ◽  
Terminal Domain ◽  
C Terminus ◽  
Common Motif ◽  
The Common

VqsR is a quorum-sensing (QS) transcriptional regulator which controls QS systems (las,rhlandpqs) by directly downregulating the expression ofqscRinPseudomonas aeruginosa. As a member of the LuxR family of proteins, VqsR shares the common motif of a helix–turn–helix (HTH)-type DNA-binding domain at the C-terminus, while the function of its N-terminal domain remains obscure. Here, the crystal structure of the N-terminal domain of VqsR (VqsR-N; residues 1–193) was determined at a resolution of 2.1 Å. The structure is folded into a regular α–β–α sandwich topology, which is similar to the ligand-binding domain (LBD) of the LuxR-type QS receptors. Although their sequence similarity is very low, structural comparison reveals that VqsR-N has a conserved enclosed cavity which could recognize acyl-homoserine lactones (AHLs) as in other LuxR-type AHL receptors. The structure suggests that VqsR could be a potential AHL receptor.

scholarly journals A Computational Strategy for Protein Function Assignment which Addresses the Multidomain Problem

2002 ◽  
Vol 3 (5) ◽  
pp. 423-440 ◽  
Author(s):  
A. J. Pérez ◽  
A. Rodríguez ◽  
O. Trelles ◽  
G. Thode
Keyword(s):  
Protein Function ◽  
Sequence Similarity ◽  
Protein Database ◽  
Specific Sequence ◽  
Functional Annotations ◽  
Cluster Set ◽  
Sequence Position ◽  
Computational Strategy ◽  
Function Assignment

A method for assigning functions to unknown sequences based on finding correlations between short signals and functional annotations in a protein database is presented. This approach is based on keyword (KW) and feature (FT) information stored in the SWISS-PROT database. The former refers to particular protein characteristics and the latter locates these characteristics at a specific sequence position. In this way, a certain keyword is only assigned to a sequence if sequence similarity is found in the position described by the FT field. Exhaustive tests performed over sequences with homologues (cluster set) and without homologues (singleton set) in the database show that assigning functions is much ’cleaner’ when information about domains (FT field) is used, than when only the keywords are used.

scholarly journals Simplified geometric representations of protein structures identify complementary interaction interfaces

2019 ◽  
Author(s):  
Caitlyn L. McCafferty ◽  
Edward M. Marcotte ◽  
David W. Taylor
Keyword(s):  
Conformational Changes ◽  
Protein Interaction ◽  
Protein Function ◽  
Large Scale ◽  
Predictive Accuracy ◽  
Protein Complexes ◽  
Protein Structures ◽  
Molecular Properties ◽  
3D Structures ◽  
Geometric Representations

ABSTRACTProtein-protein interactions are critical to protein function, but three-dimensional (3D) arrangements of interacting proteins have proven hard to predict, even given the identities and 3D structures of the interacting partners. Specifically, identifying the relevant pairwise interaction surfaces remains difficult, often relying on shape complementarity with molecular docking while accounting for molecular motions to optimize rigid 3D translations and rotations. However, such approaches can be computationally expensive, and faster, less accurate approximations may prove useful for large-scale prediction and assembly of 3D structures of multi-protein complexes. We asked if a reduced representation of protein geometry retains enough information about molecular properties to predict pairwise protein interaction interfaces that are tolerant of limited structural rearrangements. Here, we describe a cuboid transformation of 3D protein accessible surfaces on which molecular properties such as charge, hydrophobicity, and mutation rate can be easily mapped, implemented in the MorphProt package. Pairs of surfaces are compared to rapidly assess partner-specific potential surface complementarity. On two available benchmarks of 85 overall known protein complexes, we observed F1 scores (a weighted combination of precision and recall) of 19-34% at correctly identifying protein interaction surfaces, comparable to more computationally intensive 3D docking methods in the annual Critical Assessment of PRedicted Interactions. Furthermore, we examined the effect of molecular motion through normal mode simulation on a benchmark receptor-ligand pair and observed no marked loss of predictive accuracy for distortions of up to 6 Å RMSD. Thus, a cuboid transformation of protein surfaces retains considerable information about surface complementarity, offers enhanced speed of comparison relative to more complex geometric representations, and exhibits tolerance to conformational changes.

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