Video Experimental Relacionado

Updated: Mar 12, 2026

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation

Published on: May 20, 2020

Cambios en la dinámica del EGFR durante la activación en las membranas nativas según lo revelado por RMN

Mohammed Kaplan¹, Siddarth Narasimhan¹, Cecilia de Heus²

¹NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, the Netherlands.

|November 15, 2016

Resumen

La activación del receptor del factor de crecimiento epidérmico (EGFR) implica cambios dinámicos. La unión del ligando al EGFR restringe el movimiento, promoviendo la dimerización del receptor y la activación de la quinasa, crucial para la terapia contra el cáncer.

Área de la Ciencia:

La bioquímica
Biología estructural
Biofísica molecular

Sus antecedentes:

El receptor del factor de crecimiento epidérmico (EGFR) es un objetivo clave en el tratamiento del cáncer.
La comprensión de los mecanismos de activación del EGFR es crucial para desarrollar tratamientos efectivos.

Objetivo del estudio:

Investigar las propiedades estructurales y dinámicas de la activación del EGFR por el factor de crecimiento epidérmico (EGF) en membranas nativas.
Aclarar el papel de la unión de ligandos en los cambios conformacionales del EGFR.

Principales métodos:

Espectroscopia de resonancia magnética nuclear de estado sólido (SSNMR).
Mejora de la polarización nuclear dinámica (DNP).
Análisis de los estados libres de ligando y ligando del EGFR.

Principales resultados:

El dominio extracelular del EGFR libre de ligandos (ECD) es altamente dinámico, mientras que el dominio de la quinasa intracelular (KD) es rígido.
La vinculación del FEAG restringe el movimiento tanto en las regiones de ECD como en la terminal C.
La reducción de la entropía conformacional en la ECD al unirse al ligando facilita la dimerización del receptor.

Conclusiones:

Los cambios conformacionales inducidos por ligandos en el EGFR son esenciales para su activación alosterica.
Los hallazgos proporcionan información sobre los mecanismos moleculares de la señalización del EGFR.
Este estudio ofrece una nueva perspectiva sobre la dinámica de activación del EGFR relevante para el desarrollo de fármacos contra el cáncer.

Palabras clave:

El Fondo Europeo de Desarrollo Regional La RMN RMN en estado sólido activación el cáncer Proteínas de membrana el receptor La tirosina quinasa

Más Videos Relacionados

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

Published on: August 17, 2022

Oligomerization Dynamics of Cell Surface Receptors in Living Cells by Total Internal Reflection Fluorescence Microscopy Combined with Number and Brightness Analysis

Oligomerization Dynamics of Cell Surface Receptors in Living Cells by Total Internal Reflection Fluorescence Microscopy Combined with Number and Brightness Analysis

Published on: November 6, 2019

Videos de Conceptos Relacionados

Enzyme-linked Receptors

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...

MAPK Signaling Cascades

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...

Activation and Inactivation of G Proteins

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...

Transducer Mechanism: Enzyme-Linked Receptors

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:

Activation of Integrins

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...

Mitogens and the Cell Cycle

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...