Video Experimental Relacionado
Updated: Jan 12, 2026
10:27
In Vitro Differentiation of Mouse Granulocyte-macrophage-colony-stimulating Factor GM-CSF-producing T Helper THGM Cells
Published on: September 10, 2018
7.6K
La estructura del complejo receptor GM-CSF revela un modo distinto de activación del receptor de citoquinas
Guido Hansen1, Timothy R Hercus, Barbara J McClure
1Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia.
Cell
|August 12, 2008
Resumen
La estructura cristalina revela que los receptores del factor estimulante de colonias de granulocitos y macrófagos (GM-CSF) forman dodecámaras para la señalización. Este descubrimiento es clave para comprender la activación de los receptores y desarrollar nuevas terapias para enfermedades relacionadas.
Área de la Ciencia:
- Biología molecular La biología molecular.
- La señalización celular de las células.
- Biología estructural Biología estructural.
Sus antecedentes:
- El factor estimulante de colonias de granulocitos-macrófagos (GM-CSF) es una citocina vital que regula la producción y la función de las células sanguíneas.
- La desregulación del GM-CSF está implicada en la artritis reumatoide y la leucemia, mientras que tiene potencial terapéutico para otras afecciones.
- Los receptores GM-CSF son heterodímeros compuestos por una subunidad alfa específica y una subunidad beta-c compartida, pero el mecanismo de iniciación de la señalización no está claro.
Objetivo del estudio:
- Para aclarar la base estructural de la activación y señalización del receptor GM-CSF.
- Para investigar el mecanismo de ensamblaje del complejo receptor GM-CSF/GM-CSF.
- Proporcionar información para el desarrollo de nuevas terapias dirigidas a las vías de señalización GM-CSF.
Principales métodos:
- Se utilizó la cristalografía de rayos X para determinar la estructura del complejo ternario del receptor GM-CSF/GM-CSF humano.
- Se empleó la mutagénesis dirigida al sitio para investigar el papel de la interfaz dodecámara en la función del receptor.
- Se realizaron ensayos funcionales para evaluar la activación del receptor y la señalización posterior.
Principales resultados:
- La estructura cristalina reveló el montaje inesperado del complejo receptor GM-CSF/GM-CSF en estructuras dodecaméricas o de orden superior.
- Los estudios de mutagenesis confirmaron que la formación de dodecameros en la interfaz del receptor es esencial para la activación del receptor.
- Los experimentos funcionales demostraron una correlación directa entre la formación de dodecámara y la iniciación de la señalización aguas abajo.
Conclusiones:
- La activación del receptor GM-CSF depende de la formación de complejos dodecaméricos de orden superior.
- Este nuevo mecanismo de ensamblaje de receptores proporciona un marco estructural para comprender la señalización de los receptores GM-CSF, IL-3 e IL-5.
- Los hallazgos ofrecen una base para diseñar terapias dirigidas para enfermedades que involucran estas vías de señalización de citoquinas.
Más Videos Relacionados
06:56A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4
Published on: March 10, 2018
14.4K
07:45A Cell Free Assay System Estimating the Neutralizing Capacity of GM-CSF Antibody using Recombinant Soluble GM-CSF Receptor
Published on: June 27, 2011
13.0K
Videos de Conceptos Relacionados
01:20The JAK-STAT Signaling Pathway
11.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
11.9K
01:15G Protein-coupled Receptors
16.4K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
16.4K
01:30Transducer Mechanism: G Protein–Coupled Receptors
3.9K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
3.9K
01:30Assembly of Signaling Complexes
6.4K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.4K
01:22Activation and Inactivation of G Proteins
10.8K
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...
10.8K
01:21G-protein Coupled Receptors
131.4K
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
131.4K