Browse
Submit Data
Databases
API
Help

Dataset Information

30 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Detection of secondary and supersecondary structures of proteins from cryo-electron microscopy.

ABSTRACT: Recent advances in three-dimensional electron microscopy (3D EM) have enabled the quantitative visualization of the structural building blocks of proteins at improved resolutions. We provide algorithms to detect the secondary structures (?-helices and ?-sheets) from proteins for which the volumetric maps are reconstructed at 6-10? resolution. Additionally, we show that when the resolution is coarser than 10?, some of the supersecondary structures can be detected from 3D EM maps. For both these algorithms, we employ tools from computational geometry and differential topology, specifically the computation of stable/unstable manifolds of certain critical points of the distance function induced by the molecular surface. Our results connect mathematically well-defined constructions with bio-chemically induced structures observed in proteins.

SUBMITTER: Bajaj C

PROVIDER: S-EPMC3312805 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Detection of secondary and supersecondary structures of proteins from cryo-electron microscopy.

Bajaj Chandrajit C Goswami Samrat S Zhang Qin Q

Journal of structural biology 20111213 2

Recent advances in three-dimensional electron microscopy (3D EM) have enabled the quantitative visualization of the structural building blocks of proteins at improved resolutions. We provide algorithms to detect the secondary structures (α-helices and β-sheets) from proteins for which the volumetric maps are reconstructed at 6-10Å resolution. Additionally, we show that when the resolution is coarser than 10Å, some of the supersecondary structures can be detected from 3D EM maps. For both these a ...[more]

PMID: 22186625

Similar Datasets

Cryo-electron microscopy analysis of small membrane proteins.

Project description:Recent advances in single-particle cryogenic-electron microscopy have facilitated an exponential growth in the number of membrane protein structures determined to close to atomic resolution. Nevertheless, despite improvements in microscope hardware, cryo-EM software and sample preparation techniques, challenges remain for structural analysis of small-sized membrane proteins (i.e.<150 kilodalton). Here we discuss recent examples of structures of macromolecules from this category determined by cryo-EM. We analyze the underlying difficulties, the enabling technologies such as the use of antibody fragments to gain size and provide fiducials for particle alignment, and the unresolved issues like dislocation of complexes at the air-water interface. Finally, we briefly highlight the biological relevance of some of these success stories, and our predictions for the future.

| S-EPMC7665978 | biostudies-literature

Cryo-Electron Microscopy Structures of the <i>Pneumoviridae</i> Polymerases.

Project description:The resolution revolution of cryo-electron microscopy (cryo-EM) has made a significant impact on the structural analysis of the Pneumoviridae multifunctional RNA polymerases. In recent months, several high-resolution structures of apo RNA polymerases of Pneumoviridae, which includes the human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV), have been determined by single-particle cryo-EM. These structures illustrated high similarities and minor differences between the Pneumoviridae polymerases and revealed the potential mechanisms of the Pneumoviridae RNA synthesis.

| S-EPMC8020502 | biostudies-literature

Role of Backbone Dipole Interactions in the Formation of Secondary and Supersecondary Structures of Proteins.

Project description:We present a generic solvated coarse-grained protein model that can be used to characterize the driving forces behind protein folding. Each amino acid is coarse-grained with two beads, a backbone, and a side chain. Although the backbone beads are modeled as polar entities, side chains are hydrophobic, polar, or charged, thus allowing the exploration of how sequence patterning determines a protein fold. The change in orientation of the atoms of the coarse-grained unit is captured by the addition of two oppositely charged dummy particles inside the backbone coarse-grained bead. These two dummy charges represent a dipole that can fluctuate, thus introducing structural polarization into the coarse-grained model. Realistic ?/? content is achieved de novo without any biases in the force field toward a particular secondary structure. The dipoles created by the dummy particles interact with each other and drive the protein models to fold into unique structures depending on the amino acid patterning and presence of capping residues. We have also characterized the role of dipole-dipole and dipole-charge interactions in shaping the secondary and supersecondary structure of proteins. Formation of helix bundles and ?-strands are also discussed.

| S-EPMC4053078 | biostudies-literature

Building de novo cryo-electron microscopy structures collaboratively with citizen scientists.

Project description:With the rapid improvement of cryo-electron microscopy (cryo-EM) resolution, new computational tools are needed to assist and improve upon atomic model building and refinement options. This communication demonstrates that microscopists can now collaborate with the players of the computer game Foldit to generate high-quality de novo structural models. This development could greatly speed the generation of excellent cryo-EM structures when used in addition to current methods.

| S-EPMC6850521 | biostudies-literature

Atomic Resolution Structures of Human Bufaviruses Determined by Cryo-Electron Microscopy.

Project description:Bufavirus strain 1 (BuV1), a member of the Protoparvovirus genus of the Parvoviridae, was first isolated from fecal samples of children with acute diarrhea in Burkina Faso. Since this initial discovery, BuVs have been isolated in several countries, including Finland, the Netherlands, and Bhutan, in pediatric patients exhibiting similar symptoms. Towards their characterization, the structures of virus-like particles of BuV1, BuV2, and BuV3, the current known genotypes, have been determined by cryo-electron microscopy and image reconstruction to 2.84, 3.79, and 3.25 Å, respectively. The BuVs, 65-73% identical in amino acid sequence, conserve the major viral protein, VP2, structure and general capsid surface features of parvoviruses. These include a core β-barrel (βB-βI), α-helix A, and large surface loops inserted between these elements in VP2. The capsid contains depressions at the icosahedral 2-fold and around the 5-fold axes, and has three separated protrusions surrounding the 3-fold axes. Structure comparison among the BuVs and to available parvovirus structures revealed capsid surface variations and capsid 3-fold protrusions that depart from the single pinwheel arrangement of the animal protoparvoviruses. These structures provide a platform to begin the molecular characterization of these potentially pathogenic viruses.

| S-EPMC5795435 | biostudies-literature

Near-atomic cryo-electron microscopy structures of varicella-zoster virus capsids.

Project description:Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits. The VZV capsid has high thermal stability, although with relatively fewer intra- and inter-capsid protein interactions and less stably associated tegument proteins compared with other human herpesviruses. Analysis with antibodies targeting the N and C termini of the VZV SCP indicates that the hexon-capping SCP-the largest among human herpesviruses-uses its N-terminal half to bridge hexon MCP subunits and possesses a C-terminal flexible half emanating from the inner rim of the upper hexon channel into the tegument layer. Correlation of these structural features and functional observations provide insights into VZV assembly and pathogenesis and should help efforts to engineer gene delivery and anticancer vectors based on the currently available VZV vaccine.

| S-EPMC7677223 | biostudies-literature

Cryo-electron microscopy study of bacteriophage T4 displaying anthrax toxin proteins.

Project description:The bacteriophage T4 capsid contains two accessory surface proteins, the small outer capsid protein (Soc, 870 copies) and the highly antigenic outer capsid protein (Hoc, 155 copies). As these are dispensable for capsid formation, they can be used for displaying proteins and macromolecular complexes on the T4 capsid surface. Anthrax toxin components were attached to the T4 capsid as a fusion protein of the N-terminal domain of the anthrax lethal factor (LFn) with Soc. The LFn-Soc fusion protein was complexed in vitro with Hoc(-)Soc(-)T4 phage. Subsequently, cleaved anthrax protective antigen heptamers (PA63)(7) were attached to the exposed LFn domains. A cryo-electron microscopy study of the decorated T4 particles shows the complex of PA63 heptamers with LFn-Soc on the phage surface. Although the cryo-electron microscopy reconstruction is unable to differentiate on its own between different proposed models of the anthrax toxin, the density is consistent with a model that had predicted the orientation and position of three LFn molecules bound to one PA63 heptamer.

| S-EPMC2062529 | biostudies-literature

Unique structures in a tumor herpesvirus revealed by cryo-electron tomography and microscopy.

Project description:Gammaherpesviruses, including the human pathogens Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, are causative agents of lymphomas and other malignancies. The structural characterization of these viruses has been limited due to difficulties in obtaining adequate amount of virion particles. Here we report the first three-dimensional structural characterization of a whole gammaherpesvirus virion by an emerging integrated approach of cryo-electron tomography combined with single-particle cryo-electron microscopy, using murine gammaherpesvirus-68 (MHV-68) as a model system. We found that the MHV-68 virion consists of distinctive envelope and tegument compartments, and a highly conserved nucleocapsid. Two layers of tegument are identified: an inner tegument layer tethered to the underlying capsid and an outer, flexible tegument layer conforming to the overlying, pleomorphic envelope, consistent with the sequential viral tegumentation process inside host cells. Surprisingly, comparison of the MHV-68 virion and capsid reconstructions shows that the interactions between the capsid and inner tegument proteins are completely different from those observed in alpha and betaherpesviruses. These observations support the notion that the inner layer tegument across different subfamilies of herpesviruses has evolved significantly to confer specific characteristics related to viral-host interactions, in contrast to a highly conserved capsid for genome encapsidation and protection.

| S-EPMC2714863 | biostudies-literature

A Histogram-based Outlier Profile for Atomic Structures Derived from Cryo-Electron Microscopy.

Project description:As more atomic structures are determined from cryo-electron microscopy (cryo-EM) density maps, validation of such structures is an important task. We report findings after analyzing the change of cryo-EM structures in a comparison between those released by December 2016 and those released between 2017 and 2019. The cryo-EM models created from density maps with resolution better than 6 Å were divided into six data sets. A histogram-based outlier score (HBOS) was implemented and validation reports were collected from the Protein Data Bank. The results suggest that the overall quality of EM structures released after December 2016 is better than that of structures released before 2017. The conformation qualities of most residue types might have been improved, except for Leucine, Phenylalanine, and Serine in high-resolution datasets (higher than 4 Å). We observe that structures solved from 0-4 Å resolution density maps have an almost identical HBOS profile as that of structures derived from density maps with 4-6 Å resolution.

| S-EPMC9279010 | biostudies-literature

Cryo-electron microscopy structures and progress toward a dynamic understanding of KATP channels.

Project description:Adenosine triphosphate (ATP)-sensitive K+ (KATP) channels are molecular sensors of cell metabolism. These hetero-octameric channels, comprising four inward rectifier K+ channel subunits (Kir6.1 or Kir6.2) and four sulfonylurea receptor (SUR1 or SUR2A/B) subunits, detect metabolic changes via three classes of intracellular adenine nucleotide (ATP/ADP) binding site. One site, located on the Kir subunit, causes inhibition of the channel when ATP or ADP is bound. The other two sites, located on the SUR subunit, excite the channel when bound to Mg nucleotides. In pancreatic β cells, an increase in extracellular glucose causes a change in oxidative metabolism and thus turnover of adenine nucleotides in the cytoplasm. This leads to the closure of KATP channels, which depolarizes the plasma membrane and permits Ca2+ influx and insulin secretion. Many of the molecular details regarding the assembly of the KATP complex, and how changes in nucleotide concentrations affect gating, have recently been uncovered by several single-particle cryo-electron microscopy structures of the pancreatic KATP channel (Kir6.2/SUR1) at near-atomic resolution. Here, the author discusses the detailed picture of excitatory and inhibitory ligand binding to KATP that these structures present and suggests a possible mechanism by which channel activation may proceed from the ligand-binding domains of SUR to the channel pore.

| S-EPMC5940251 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data