The Dynamic Structure of the Estrogen Receptor

The estrogen receptor (ER) mediates most of the biological effects of estrogens at the level of gene regulation by interacting through its site-specific DNA and with other coregulatory proteins. In recent years, new information regarding the dynamic structural nature of ER has emerged. The physiological effects of estrogen are manifested through ER's two isoforms, ERα and ERβ. These two isoforms (ERα and ERβ) display distinct regions of sequence homology. The three-dimensional structures of the DNA-binding domain (DBD) and ligand-binding domain (LBD) have been solved, whereas no three-dimensional natively folded structure for the ER N-terminal domain (NTD) is available to date. However, insights about the structural and functional correlations regarding the ER NTD have recently emerged. In this paper, we discuss the knowledge about the structural characteristics of the ER in general and how the structural features of the two isoforms differ, and its subsequent role in gene regulation.

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Identification of fibrillogenic regions in human triosephosphate isomerase

PeerJ ◽

10.7717/peerj.1676 ◽

2016 ◽

Vol 4 ◽

pp. e1676 ◽

Cited By ~ 3

Author(s):

Edson N. Carcamo-Noriega ◽

Gloria Saab-Rincon

Keyword(s):

Triosephosphate Isomerase ◽

Structural Characteristics ◽

Three Dimensional ◽

Structural Features ◽

Structural Topology ◽

Tim Barrel ◽

Functional Amyloids ◽

Polypeptide Chains ◽

Protein Fragmentation ◽

Chain Interaction

Background.Amyloid secondary structure relies on the intermolecular assembly of polypeptide chains through main-chain interaction. According to this, all proteins have the potential to form amyloid structure, nevertheless, in nature only few proteins aggregate into toxic or functional amyloids. Structural characteristics differ greatly among amyloid proteins reported, so it has been difficult to link the fibrillogenic propensity with structural topology. However, there are ubiquitous topologies not represented in the amyloidome that could be considered as amyloid-resistant attributable to structural features, such is the case of TIM barrel topology.Methods.This work was aimed to study the fibrillogenic propensity of human triosephosphate isomerase (HsTPI) as a model of TIM barrels. In order to do so, aggregation of HsTPI was evaluated under native-like and destabilizing conditions. Fibrillogenic regions were identified by bioinformatics approaches, protein fragmentation and peptide aggregation.Results.We identified four fibrillogenic regions in the HsTPI corresponding to theβ3,β6,β7y α8 of the TIM barrel. From these, theβ3-strand region (residues 59–66) was highly fibrillogenic. In aggregation assays, HsTPI under native-like conditions led to amorphous assemblies while under partially denaturing conditions (urea 3.2 M) formed more structured aggregates. This slightly structured aggregates exhibited residual cross-βstructure, as demonstrated by the recognition of the WO1 antibody and ATR-FTIR analysis.Discussion.Despite the fibrillogenic regions present in HsTPI, the enzyme maintained under native-favoring conditions displayed low fibrillogenic propensity. This amyloid-resistance can be attributed to the three-dimensional arrangement of the protein, whereβ-strands, susceptible to aggregation, are protected in the core of the molecule. Destabilization of the protein structure may expose inner regions promotingβ-aggregation, as well as the formation of hydrophobic disordered aggregates. Being this last pathway kinetically favored over the thermodynamically more stable fibril aggregation pathway.

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Computational Study of Estrogen Receptor-Alpha Antagonist with Three-Dimensional Quantitative Structure-Activity Relationship, Support Vector Regression, and Linear Regression Methods

International Journal of Medicinal Chemistry ◽

10.1155/2013/743139 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Ying-Hsin Chang ◽

Jun-Yan Chen ◽

Chiou-Yi Hor ◽

Yu-Chung Chuang ◽

Chang-Biau Yang ◽

...

Keyword(s):

Estrogen Receptor ◽

Inhibitory Activity ◽

Estrogen Receptor Alpha ◽

Computational Study ◽

Three Dimensional ◽

Quantitative Structure Activity Relationship ◽

Structural Features ◽

Support Vector ◽

Human Estrogen Receptor ◽

Qsar Models

Human estrogen receptor (ER) isoforms, ERα and ERβ, have long been an important focus in the field of biology. To better understand the structural features associated with the binding of ERα ligands to ERα and modulate their function, several QSAR models, including CoMFA, CoMSIA, SVR, and LR methods, have been employed to predict the inhibitory activity of 68 raloxifene derivatives. In the SVR and LR modeling, 11 descriptors were selected through feature ranking and sequential feature addition/deletion to generate equations to predict the inhibitory activity toward ERα. Among four descriptors that constantly appear in various generated equations, two agree with CoMFA and CoMSIA steric fields and another two can be correlated to a calculated electrostatic potential of ERα.

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Study on Connectivity Mechanism and Robustness of Three-Dimensional Pore Network of Sandstone

Geofluids ◽

10.1155/2021/5533345 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Guannan Liu ◽

Xiaopeng Pei ◽

Dayu Ye ◽

Feng Gao ◽

Zongqing Zhou ◽

...

Keyword(s):

Porous Media ◽

Path Length ◽

Structural Characteristics ◽

Three Dimensional ◽

Ct Scanning ◽

Pore Network ◽

Structural Features ◽

Average Path Length ◽

Microscopic Mechanism ◽

Complex Network Theory

As one of the most prevalent porous media, rock contains a large number of pore throats of varying size and shape. It is essential to analyze the complex pore network structure and to define the network structural features to reveal the microscopic mechanism of the rock permeability. In this paper, based on the complex network theory and CT scanning technology, sandstone is used as an example to study the structural characteristics of the rock network with different porosities. The results show that the structural characteristics of the sandstone seepage network are consistent with BA scale-free network, whose average path length increases with the size of the network. At the same time, the porosity of the sandstone is strongly influenced by the number of throat in the rock pore network. Furthermore, our analysis concludes that a few pores with a large number of connections contribute significantly to the overall connectivity of the sandstone seepage network. Removing the ‘hub’ pores increased the average path length of the entire network by 27.63-37.26%, which could not be achieved by randomly removing method. While the sandstone seepage network has better fault tolerance and robustness to external random attacks, this study provides a new approach to study the mechanisms of fluid storage and migration in porous media.

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Structural Characteristics of Human Salivary Statherin: A Model for Boundary Lubrication at the Enamel Surface

Critical Reviews in Oral Biology & Medicine ◽

10.1177/10454411930040031501 ◽

1993 ◽

Vol 4 (3) ◽

pp. 363-370 ◽

Cited By ~ 29

Author(s):

Narayanan Ramasubbu ◽

Leonard M. Thomas ◽

Krishna K. Bhandary ◽

Michael J. Levine

Keyword(s):

Boundary Lubrication ◽

Structure Prediction ◽

Structural Model ◽

Structural Characteristics ◽

Three Dimensional ◽

Structural Features ◽

Enamel Surface ◽

Binding Region ◽

Binding Ability ◽

Oriented Aggregation

A three-dimensional structural model for salivary statherin in aqueous phase has been developed using structure prediction, circular dichroism, molecular modeling, and mechanics. The relevant structural features of statherin are N-terminal helix segment connected to a long poly-L-proline type II segment, which is followed by a short extended structure. Using this model, the hydroxyapatite binding ability of statherin has been explained. The hydroxyapatite binding region is comprised of the N-terminal acidic residues (Asp-pSer-pSer-Glu-Glu) and Glu-26, which are clustered together in space. Partial conformational unfolding and oriented aggregation of several statherin molecules at the enamel surface provides an amphipathic film that is responsible for the boundary lubrication exhibited by statherin.

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Three-dimensional visualization and characterization of paper machine felts and their relationship to their properties and dewatering performance

TAPPI Journal ◽

10.32964/tj20.7.23 ◽

2021 ◽

Vol 20 (7) ◽

pp. 423-435

Author(s):

CAROLINE FRISCHMON ◽

JOHN XU ◽

SHRI RAMASWAMY

Keyword(s):

Size Distribution ◽

Structural Characteristics ◽

Three Dimensional ◽

Structural Features ◽

Chemical Compositions ◽

Water Removal ◽

Paper Machine ◽

Machine Direction ◽

Paper Properties ◽

Permeability Characteristics

Polymeric felts are commonly used in the papermaking process on the paper machine wet end, in the press section, and in the dryer section. They provide an important function during paper manufacturing, including as a carrier or support; as a filter media assisting with water removal on the paper machine; in retention of fibers, fines, and fillers; and in some applications, such as tissue and towel, to impart key structural features to the web. These felts can have highly interwoven complex internal structures comprised of machine direction and cross-machine direction yarns of varying sizes and chemical compositions. Here, we present a non-intrusive three-dimensional (3D) image visualization method using advanced X-ray computed tomography (XRCT). This method was used to characterize the complex 3D felt structure and determine the water removal characteristics of some commonly used paper machine felts. The structural features analyzed include porosity; specific pore-yarn interfacial surface area; 3D pore size distribution; 3D fiber or yarn-size distribution; and their variations through the thickness direction. The top, middle, and bottom layers of the felt have very different structures to assist with water removal and impart paper properties. The size distribution of the yarns, as well as the pores in the different layers of the felt, are also inherently different. These structural features were non-intrusively quantified. In addition, variation in the structural characteristics through the thickness of the felts and its potential role in papermaking is explored. In addition to the 3D structural characteristics, permeability characteristics and water removal characteristics, including rewetting of select felt samples, have also been experimentally determined. It is interesting to observe the relationship between key structural features and permeability and water removal characteristics. These relationships can provide additional insights into press felt design, as well as ways to improve product properties and the dewatering efficiency and productivity of the paper machine.

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MicroCT as a Useful Tool for Analysing the 3D Structure of Lichens and Quantifying Internal Cephalodia in Lobaria pulmonaria

Applied Microbiology ◽

10.3390/applmicrobiol1020015 ◽

2021 ◽

Vol 1 (2) ◽

pp. 189-200

Author(s):

Julia Gerasimova ◽

Bernhard Ruthensteiner ◽

Andreas Beck

Keyword(s):

High Resolution ◽

Computer Tomography ◽

Structural Characteristics ◽

3D Structure ◽

Three Dimensional ◽

Structural Features ◽

Lobaria Pulmonaria ◽

X Ray ◽

Yield Information ◽

Non Destructive

High-resolution X-ray computer tomography (microCT) is a well-established technique to analyse three-dimensional microstructures in 3D non-destructive imaging. The non-destructive three-dimensional analysis of lichens is interesting for many reasons. The examination of hidden structural characteristics can, e.g., provide information on internal structural features (form and distribution of fungal-supporting tissue/hypha), gas-filled spaces within the thallus (important for gas exchange and, thus, physiological processes), or yield information on the symbiont composition within the lichen, e.g., the localisation and amount of additional cyanobacteria in cephalodia. Here, we present the possibilities and current limitations for applying conventional laboratory-based high-resolution X-ray computer tomography to analyse lichens. MicroCT allows the virtual 3D reconstruction of a sample from 2D X-ray projections and is helpful for the non-destructive analysis of structural characters or the symbiont composition of lichens. By means of a quantitative 3D image analysis, the volume of internal cephalodia is determined for Lobaria pulmonaria and the external cephalodia of Peltigera leucophlebia. Nevertheless, the need for higher-resolution tomography for more detailed studies is emphasised. Particular challenges are the large sizes of datasets to be analysed and the high variability of the lichen microstructures.

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Steroids and the Scientist

Molecular Endocrinology ◽

10.1210/me.2004-0479 ◽

2005 ◽

Vol 19 (6) ◽

pp. 1412-1417 ◽

Cited By ~ 12

Author(s):

Jan-Åke Gustafsson

Keyword(s):

Estrogen Receptor ◽

Dna Binding ◽

Domain Structure ◽

Three Dimensional ◽

Binding Domain ◽

Cholesterol Homeostasis ◽

Estrogen Receptor Β ◽

Orphan Receptor ◽

Estrogen Signaling ◽

Dna Binding Domain

Abstract Our interest in nuclear receptors (NRs) originated from early studies on hepatic steroid metabolism. We discovered a new hypothalamo-pituitary-liver axis, imprinted neonatally by androgens and operating through sexually differentiated GH secretory patterns. Male and female patterns have opposite effects on sexually differentiated hepatic genes, explaining sexually dimorphic liver patterns. To further understand steroid action, we purified the glucocorticoid receptor (GR) leading to our discovery of the NR three-domain structure, with separable DNA binding domain and ligand binding domains and a third domain now known to have transcriptional regulatory properties. Knowledge of this domain structure has been immensely important for deciphering NR actions. Using this first purified NR, we collaborated with Keith Yamamoto and first demonstrated specific NR binding to DNA. This also was the first demonstration of a mammalian transcription factor, a breakthrough that led to discovery of NR response elements. In further collaboration with Yamamoto, we cloned the first NR cDNA sequences, leading to cloning of the superfamily of NR genes. With Yamamoto and Kaptein, we determined the first three-dimensional NR structure, that of DNA binding domain. Later work on orphan receptors resulted in the first discovery of: 1) endogenous ligands for an orphan receptor (fatty acids as activators of peroxisomal proliferator-activated receptor α); 2) liver X receptor β (OR-1) and its role in central nervous system cholesterol homeostasis; and 3) estrogen receptor β, leading to a paradigm shift in understanding of estrogen signaling, of importance in endocrinology, immunology, and oncology and to development of estrogen receptor β agonists for treatment of autoimmune diseases, prostate disease, depression, and ovulatory dysfunction.

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Methods for making stereoslides and -prints, with freeze-etched olfactory epithelium as example

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100113408 ◽

1984 ◽

Vol 42 ◽

pp. 704-705

Author(s):

Bert Ph. M. Menco ◽

Ido F. Menco ◽

Frans L.T. Verdonk

Keyword(s):

Electron Microscope ◽

Olfactory Epithelium ◽

Three Dimensional ◽

Supporting Cell ◽

Structural Features ◽

Extensive Study ◽

Sprague Dawley ◽

Freezing Method ◽

Respiratory Epithelia ◽

Three Dimensional Presentation

Previously we presented an extensive study of the distributions of intramembranous particles of structures in apical surfaces of nasal olfactory and respiratory epithelia of the Sprague-Dawley rat. For the same structures these distributions were compared in samples which were i) chemically fixed and cryo-protected with glycerol before cryo-fixation, after excision, and ii)ultra-rapidly frozen by means of the slam-freezing method. Since a three-dimensional presentation markedly improves visualization of structural features micrographs were presented as stereopairs. Two exposures were made by tiling the sample stage of the electron microscope 6° in either direction with an eucentric goniometer. The negatives (Agfa Pan 25 Professional) were reversed with Kodak Technical Pan Film 2415 developed in D76 1:1. The prints were made from these reversed negatives. As an example tight-junctional features of an olfactory supporting cell in a region where this cell conjoined with two other cells are presented (Fig. 1).

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