Video Experimental Relacionado

Updated: Jul 9, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Determinantes de la especificidad del gen objetivo para los receptores de esteroides / hormonas tiroideas

K Umesono¹, R M Evans

¹Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92037.

|June 30, 1989

Resumen

Los investigadores alteraron los receptores hormonales para cambiar su especificidad de unión al ADN. Algunos cambios en los aminoácidos transformaron los receptores glucocorticoides en receptores de estrógeno o hormonas tiroideas, revelando determinantes estructurales clave.

Área de la Ciencia:

Biología molecular La biología molecular.
Endocrinología Endocrinología.
Genética La genética.

Sus antecedentes:

Las hormonas esteroideas y tiroideas regulan la expresión génica a través de sitios específicos de unión al ADN llamados elementos de respuesta hormonal (HREs).
La especificidad del receptor está determinada por las interacciones con los HREs, que varían en la secuencia de nucleótidos y el espaciado de medio sitio.

Objetivo del estudio:

Investigar los determinantes estructurales del reconocimiento del elemento de respuesta hormonal (HRE) por los receptores nucleares.
Comprender cómo los dominios de unión al ADN del receptor evolucionan y confieren especificidad genética objetivo.

Principales métodos:

Se utilizó la mutagenesis dirigida al sitio para alterar los aminoácidos dentro de los dominios del dedo de zinc de los receptores nucleares.
Los receptores modificados fueron probados por su capacidad para unirse a diferentes secuencias de HRE.

Principales resultados:

El cambio de tres aminoácidos en el primer dedo de zinc convirtió la especificidad del receptor glucocorticoide en la especificidad del receptor de estrógeno.
Un solo cambio de aminoácido (de Gly a Glu) permitió el reconocimiento de los elementos de respuesta de glucocorticoides y estrógenos.
La alteración de cinco aminoácidos en el segundo dedo de zinc confirió especificidad al receptor de la hormona tiroidea.

Conclusiones:

Los aminoácidos específicos en los dominios del dedo de zinc son críticos para discriminar la secuencia de HRE y el espaciado de medio sitio.
Estos hallazgos proporcionan información sobre la evolución de la unión del ADN de los receptores nucleares y las redes de genes receptores hormonales.

Más Videos Relacionados

Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation

Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation

Published on: February 10, 2023

In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse

In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse

Published on: October 6, 2023

Videos de Conceptos Relacionados

Intracellular Hormone Receptors

Intracellular Hormone Receptors

Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell

Internal Receptors

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.

Transducer Mechanism: Nuclear Receptors

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:

Target Cell Response to Hormones

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...