Video Experimental Relacionado
Updated: Mar 6, 2026
05:48
Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
Published on: January 2, 2018
8.0K
La estructura del complejo notch-Jagged implica un enlace de captura en la sintonización de la sensibilidad del
Vincent C Luca1,2, Byoung Choul Kim3,4, Chenghao Ge5
1Departments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Science (New York, N.Y.)
|March 4, 2017
Resumen
La activación del receptor de muesca se basa en la fuerza mecánica y la glicosilación. Los nuevos datos estructurales revelan cómo la unión de Jagged1 a Notch1 utiliza estas fuerzas para regular las decisiones del destino celular.
Área de la Ciencia:
- Biología celular
- Biología estructural
- La bioquímica
Sus antecedentes:
- La señalización de la muesca es crucial para la determinación del destino celular.
- Esta vía es única en su dependencia de las fuerzas mecánicas y la glicosilación de proteínas.
- Comprender las interacciones moleculares es clave para descifrar la regulación de la vía de Notch.
Objetivo del estudio:
- Para aclarar la base estructural de la interacción entre Notch1 y Jagged1 (Jag1).
- Investigar el papel de la fuerza mecánica y la glicosilación en la unión Notch1-Jag1.
- Para comparar la unión de Notch1 a Jag1 frente a los ligandos de tipo Delta 4 (DLL4).
Principales métodos:
- Cristalografía de rayos X con una resolución de 2,5 angstroms.
- Análisis de las interfaces de unión proteína-proteína.
- Caracterización de las modificaciones de la glicosilación de proteínas (fucosa enlazada con O).
Principales resultados:
- Se determinó una estructura detallada del complejo extracelular Notch1-Jag1.
- La fucosa enlazada con O en los dominios 8 y 12 del EGF de Notch1 interactúa con los dominios Jag1 del EGF3 y C2.
- Jag1 exhibe un comportamiento de enlace de captura sobre la unión de Notch1, influenciado por fuerzas mecánicas.
- Notch1 utiliza diferentes dominios para la unión Jag1 en comparación con la unión DLL4.
Conclusiones:
- Las fuerzas mecánicas y los patrones específicos de glicosilación son críticos para la interacción Notch1-Jag1.
- El comportamiento de enlace de captura de Jag1 permite la regulación dependiente de la fuerza de la señalización de Notch.
- Esto proporciona un mecanismo para la discriminación de ligandos y la potenciación de la señalización de Notch a través de señales mecánicas.
Videos de Conceptos Relacionados
03:14Notch Signaling Pathway
6.8K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
6.8K
02:40Ligand Binding Sites
15.5K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.5K
02:40Ligand Binding Sites
9.0K
9.0K
02:58Crystal Field Theory - Octahedral Complexes
31.4K
Crystal Field Theory
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
31.4K
02:42Valence Bond Theory
11.4K
Coordination compounds and complexes exhibit different colors, geometries, and magnetic behavior, depending on the metal atom/ion and ligands from which they are composed. In an attempt to explain the bonding and structure of coordination complexes, Linus Pauling proposed the valence bond theory, or VBT, using the concepts of hybridization and the overlapping of the atomic orbitals. According to VBT, the central metal atom or ion (Lewis acid) hybridizes to provide empty orbitals of suitable...
11.4K
01:49Conserved Binding Sites
5.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.2K