scholarly journals Capturing the complexity of topologically associating domains through multi-feature optimization

2021 ◽  
Author(s):  
Natalie Sauerwald ◽  
Carl Kingsford
Keyword(s):  
Binding Sites ◽  
Three Dimensional ◽  
Replication Timing ◽  
Biological Properties ◽  
Ctcf Binding ◽  
Dimensional Structure ◽  
Biological Targets ◽  
Topologically Associating Domains ◽  
Contact Frequency ◽  
Algorithmic Framework

AbstractThe three-dimensional structure of human chromosomes is tied to gene regulation and replication timing, but there is still a lack of consensus on the computational and biological definitions for chromosomal substructures such as topologically associating domains (TADs). TADs are described and identified by various computational properties leading to different TAD sets with varying compatibility with biological properties such as boundary occupancy of structural proteins. We unify many of these computational and biological targets into one algorithmic framework that jointly maximizes several computational TAD definitions and optimizes TAD selection for a quantifiable biological property. Using this framework, we explore the variability of TAD sets optimized for six different desirable properties of TAD sets: high occupancy of CTCF, RAD21, and H3K36me3 at boundaries, reproducibility between replicates, high intra- vs inter-TAD difference in contact frequencies, and many CTCF binding sites at boundaries. The compatibility of these biological targets varies by cell type, and our results suggest that these properties are better reflected as subpopulations or families of TADs rather than a singular TAD set fitting all TAD definitions and properties. We explore the properties that produce similar TAD sets (reproducibility and inter- vs intra-TAD difference, for example) and those that lead to very different TADs (such as CTCF binding sites and inter- vs intra-TAD contact frequency difference).

scholarly journals Systematic Chromatin Architecture Analysis in Xenopus tropicalis Reveals Conserved Three-Dimensional Folding Principles of Vertebrate Genomes

2020 ◽  
Author(s):  
Longjian Niu ◽  
Wei Shen ◽  
Zhaoying Shi ◽  
Na He ◽  
Jing Wan ◽  
...  
Keyword(s):  
Binding Sites ◽  
Three Dimensional ◽  
Xenopus Tropicalis ◽  
Ctcf Binding ◽  
Interphase Nuclei ◽  
Chromosome Architecture ◽  
Topologically Associating Domains ◽  
Genome Activation ◽  
Zygotic Genome ◽  
Architecture Analysis

ABSTRACTMetazoan genomes are folded into 3D structures in interphase nuclei. However, the molecular mechanism remains unknown. Here, we show that topologically associating domains (TADs) form in two waves during Xenopus tropicalis embryogenesis, first at zygotic genome activation and then as the expression of CTCF and Rad21 is elevated. We also found TAD structures continually change for at least three times during development. Surprisingly, the directionality index is preferentially stronger on one side of TADs where orientation-biased CTCF and Rad21 binding are observed, a conserved pattern that is found in human cells as well. Depletion analysis revealed CTCF, Rad21, and RPB1, a component of RNAPII, are required for the establishment of TADs. Overall, our work shows that Xenopus is a powerful model for chromosome architecture analysis. Furthermore, our findings indicate that cohesin-mediated extrusion may anchor at orientation-biased CTCF binding sites, supporting a CTCF-anchored extrusion model as the mechanism for TAD establishment.

Conformation of Ribosomes from Escherichia Coli

1974 ◽  
Vol 32 ◽  
pp. 210-211
Author(s):  
M. Boublik ◽  
W. Hellmann ◽  
F. Jenkins
Keyword(s):  
Binding Sites ◽  
Ribosomal Proteins ◽  
Fluorescent Dyes ◽  
Protein Biosynthesis ◽  
Three Dimensional ◽  
Spatial Arrangement ◽  
Dimensional Structure ◽  
Complete Understanding ◽  
And Function

The present knowledge of the three-dimensional structure of ribosomes is far too limited to enable a complete understanding of the various roles which ribosomes play in protein biosynthesis. The spatial arrangement of proteins and ribonuclec acids in ribosomes can be analysed in many ways. Determination of binding sites for individual proteins on ribonuclec acid and locations of the mutual positions of proteins on the ribosome using labeling with fluorescent dyes, cross-linking reagents, neutron-diffraction or antibodies against ribosomal proteins seem to be most successful approaches. Structure and function of ribosomes can be correlated be depleting the complete ribosomes of some proteins to the functionally inactive core and by subsequent partial reconstitution in order to regain active ribosomal particles.

Three Dimensional structure and organization of diploid chromosomes by optical section microscopy

1987 ◽  
Vol 45 ◽  
pp. 633-635
Author(s):  
David A. Agard ◽  
Yasushi Hiraoka ◽  
John W. Sedat
Keyword(s):  
Dimensional Space ◽  
Three Dimensional ◽  
Developmental State ◽  
Mitotic Cell ◽  
Biological Properties ◽  
Dimensional Structure ◽  
Specific Gene ◽  
Three Dimensional Structure ◽  
Complementary Techniques ◽  
Dynamic Structures

In an effort to understand the complex relationship between structure and biological function within the nucleus, we have embarked on a program to examine the three-dimensional structure and organization of Drosophila melanogaster embryonic chromosomes. Our overall goal is to determine how DNA and proteins are organized into complex and highly dynamic structures (chromosomes) and how these chromosomes are arranged in three dimensional space within the cell nucleus. Futher, we hope to be able to correlate structual data with such fundamental biological properties as stage in the mitotic cell cycle, developmental state and transcription at specific gene loci.Towards this end, we have been developing methodologies for the three-dimensional analysis of non-crystalline biological specimens using optical and electron microscopy. We feel that the combination of these two complementary techniques allows an unprecedented look at the structural organization of cellular components ranging in size from 100A to 100 microns.

scholarly journals Determination of the alpha-actinin-binding site on actin filaments by cryoelectron microscopy and image analysis.

1994 ◽  
Vol 126 (2) ◽  
pp. 433-443 ◽  
Author(s):  
A McGough ◽  
M Way ◽  
D DeRosier
Keyword(s):  
Image Analysis ◽  
Smooth Muscle ◽  
Binding Sites ◽  
Actin Filaments ◽  
Three Dimensional ◽  
Actin Binding ◽  
Dimensional Structure ◽  
Outer Face ◽  
Actin Binding Domain

The three-dimensional structure of actin filaments decorated with the actin-binding domain of chick smooth muscle alpha-actinin (alpha A1-2) has been determined to 21-A resolution. The shape and location of alpha A1-2 was determined by subtracting maps of F-actin from the reconstruction of decorated filaments. alpha A1-2 resembles a bell that measures approximately 38 A at its base and extends 42 A from its base to its tip. In decorated filaments, the base of alpha A1-2 is centered about the outer face of subdomain 2 of actin and contacts subdomain 1 of two neighboring monomers along the long-pitch (two-start) helical strands. Using the atomic model of F-actin (Lorenz, M., D. Popp, and K. C. Holmes. 1993. J. Mol. Biol. 234:826-836.), we have been able to test directly the likelihood that specific actin residues, which have been previously identified by others, interact with alpha A1-2. Our results indicate that residues 86-117 and 350-375 comprise distinct binding sites for alpha-actinin on adjacent actin monomers.

scholarly journals Xanthan Gum–Konjac Glucomannan Blend Hydrogel for Wound Healing

Polymers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 99 ◽  
Author(s):  
Andreia Alves ◽  
Sónia P. Miguel ◽  
André R.T.S. Araujo ◽  
María José de Jesús Valle ◽  
Amparo Sánchez Navarro ◽  
...  
Keyword(s):  
Xanthan Gum ◽  
Biomedical Application ◽  
Three Dimensional ◽  
High Water ◽  
Biological Properties ◽  
Konjac Glucomannan ◽  
Wound Dressings ◽  
Dimensional Structure ◽  
Future Application ◽  
High Water Content

Hydrogels are considered to be the most ideal materials for the production of wound dressings since they display a three-dimensional structure that mimics the native extracellular matrix of skin as well as a high-water content, which confers a moist environment at the wound site. Until now, different polymers have been used, alone or blended, for the production of hydrogels aimed for this biomedical application. From the best of our knowledge, the application of a xanthan gum–konjac glucomannan blend has not been used for the production of wound dressings. Herein, a thermo-reversible hydrogel composed of xanthan gum–konjac glucomannan (at different concentrations (1% and 2% w/v) and ratios (50/50 and 60/40)) was produced and characterized. The obtained data emphasize the excellent physicochemical and biological properties of the produced hydrogels, which are suitable for their future application as wound dressings.

scholarly journals TransformerCPI: improving compound–protein interaction prediction by sequence-based deep learning with self-attention mechanism and label reversal experiments

2020 ◽  
Vol 36 (16) ◽  
pp. 4406-4414 ◽  
Author(s):  
Lifan Chen ◽  
Xiaoqin Tan ◽  
Dingyan Wang ◽  
Feisheng Zhong ◽  
Xiaohong Liu ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Three Dimensional ◽  
Prediction Performance ◽  
Dimensional Structure ◽  
Sequence Information ◽  
Biological Targets ◽  
Interaction Prediction ◽  
Protein Interaction Prediction ◽  
Improved Performance ◽  
Ligand Bias

Abstract Motivation Identifying compound–protein interaction (CPI) is a crucial task in drug discovery and chemogenomics studies, and proteins without three-dimensional structure account for a large part of potential biological targets, which requires developing methods using only protein sequence information to predict CPI. However, sequence-based CPI models may face some specific pitfalls, including using inappropriate datasets, hidden ligand bias and splitting datasets inappropriately, resulting in overestimation of their prediction performance. Results To address these issues, we here constructed new datasets specific for CPI prediction, proposed a novel transformer neural network named TransformerCPI, and introduced a more rigorous label reversal experiment to test whether a model learns true interaction features. TransformerCPI achieved much improved performance on the new experiments, and it can be deconvolved to highlight important interacting regions of protein sequences and compound atoms, which may contribute chemical biology studies with useful guidance for further ligand structural optimization. Availability and implementation https://github.com/lifanchen-simm/transformerCPI.

Zona Pellucida Proteins, Fibrils, and Matrix

2020 ◽  
Vol 89 (1) ◽  
pp. 695-715
Author(s):  
Eveline S. Litscher ◽  
Paul M. Wassarman
Keyword(s):  
Extracellular Matrix ◽  
Zona Pellucida ◽  
Three Dimensional ◽  
Structural Features ◽  
Biological Properties ◽  
Preimplantation Development ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Early Embryos ◽  
N Terminus

The zona pellucida (ZP) is an extracellular matrix that surrounds all mammalian oocytes, eggs, and early embryos and plays vital roles during oogenesis, fertilization, and preimplantation development. The ZP is composed of three or four glycosylated proteins, ZP1–4, that are synthesized, processed, secreted, and assembled into long, cross-linked fibrils by growing oocytes. ZP proteins have an immunoglobulin-like three-dimensional structure and a ZP domain that consists of two subdomains, ZP-N and ZP-C, with ZP-N of ZP2 and ZP3 required for fibril assembly. A ZP2–ZP3 dimer is located periodically along ZP fibrils that are cross-linked by ZP1, a protein with a proline-rich N terminus. Fibrils in the inner and outer regions of the ZP are oriented perpendicular and parallel to the oolemma, respectively, giving the ZP a multilayered appearance. Upon fertilization of eggs, modification of ZP2 and ZP3 results in changes in the ZP's physical and biological properties that have important consequences. Certain structural features of ZP proteins suggest that they may be amyloid-like proteins.

scholarly journals Disruption of the utrophin–actin interaction by monoclonal antibodies and prediction of an actin-binding surface of utrophin

1998 ◽  
Vol 337 (1) ◽  
pp. 119-123 ◽  
Author(s):  
Glenn E. MORRIS ◽  
Nguyen thi MAN ◽  
Nguyen thi Ngoc HUYEN ◽  
Alexander PEREBOEV ◽  
John KENDRICK-JONES ◽  
...  
Keyword(s):  
Binding Sites ◽  
Three Dimensional ◽  
Binding Domain ◽  
Actin Binding ◽  
Dimensional Structure ◽  
Functional Regions ◽  
Binding Surface ◽  
Actin Binding Domain ◽  
Actin Binding Site ◽  
Helical Region

Monoclonal antibody (mAb) binding sites in the N-terminal actin-binding domain of utrophin have been identified using phage-displayed peptide libraries, and the mAbs have been used to probe functional regions of utrophin involved in actin binding. mAbs were characterized for their ability to interact with the utrophin actin-binding domain and to affect actin binding to utrophin in sedimentation assays. One of these antibodies was able to inhibit utrophin–F-actin binding and was shown to recognize a predicted helical region at residues 13–22 of utrophin, close to a previously predicted actin-binding site. Two other mAbs which did not affect actin binding recognized predicted loops in the second calponin homology domain of the utrophin actin-binding domain. Using the known three-dimensional structure of the homologous actin-binding domain of fimbrin, these results have enabled us to determine the likely orientation of the utrophin actin-binding domain with respect to the actin filament.

A new RNase sheds light on the RNase/angiogenin subfamily from zebrafish

2010 ◽  
Vol 433 (2) ◽  
pp. 345-355 ◽  
Author(s):  
Elio Pizzo ◽  
Antonello Merlino ◽  
Mimmo Turano ◽  
Irene Russo Krauss ◽  
Francesca Coscia ◽  
...  
Keyword(s):  
Functional Properties ◽  
Danio Rerio ◽  
Three Dimensional ◽  
Biological Properties ◽  
Rnase A ◽  
Dimensional Structure ◽  
Structural And Functional Properties ◽  
Sequence Signature ◽  
Bactericidal Activities ◽  
Rnase A Superfamily

Recently, extracellular RNases of the RNase A superfamily, with the characteristic CKxxNTF sequence signature, have been identified in fish. This has led to the recognition that these RNases are present in the whole vertebrate subphylum. In fact, they comprise the only enzyme family unique to vertebrates. Four RNases from zebrafish (Danio rerio) have been previously reported and have a very low RNase activity; some of these are endowed, like human angiogenin, with powerful angiogenic and bactericidal activities. In the present paper, we report the three-dimensional structure, the thermodynamic behaviour and the biological properties of a novel zebrafish RNase, ZF-RNase-5. The investigation of its structural and functional properties, extended to all other subfamily members, provides an inclusive description of the whole zebrafish RNase subfamily.

scholarly journals BiRDS - Binding Residue Detection from Protein Sequences using Deep ResNets

2021 ◽  
Author(s):  
Vineeth Chelur ◽  
U. Deva Priyakumar
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Tertiary Structure ◽  
Solvent Accessibility ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Relative Solvent Accessibility ◽  
Single Chain ◽  
Sequence Alignments ◽  
Multiple Sequence

Protein-drug interactions play important roles in many biological processes and therapeutics. Prediction of the active binding site of a protein helps discover and optimise these interactions leading to the design of better ligand molecules. The tertiary structure of a protein determines the binding sites available to the drug molecule. A quick and accurate prediction of the binding site from sequence alone without utilising the three-dimensional structure is challenging. Deep Learning has been used in a variety of biochemical tasks and has been hugely successful. In this paper, a Residual Neural Network (leveraging skip connections) is implemented to predict a protein's most active binding site. An Annotated Database of Druggable Binding Sites from the Protein DataBank, sc-PDB, is used for training the network. Features extracted from the Multiple Sequence Alignments (MSAs) of the protein generated using DeepMSA, such as Position-Specific Scoring Matrix (PSSM), Secondary Structure (SS3), and Relative Solvent Accessibility (RSA), are provided as input to the network. A weighted binary cross-entropy loss function is used to counter the substantial imbalance in the two classes of binding and non-binding residues. The network performs very well on single-chain proteins, providing a pocket that has good interactions with a ligand.

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