Video Experimental Relacionado
Updated: May 6, 2026
07:24
A Protocol for the Production of KLRG1 Tetramer
Published on: January 13, 2010
9.4K
Las estructuras de β-klotho revelan un mecanismo similar a un "código postal" para la señalización endocrina del FGF
Sangwon Lee1, Jungyuen Choi1, Jyotidarsini Mohanty1
1Department of Pharmacology and Yale Cancer Biology Institute, Yale School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.
Nature
|January 18, 2018
Resumen
Los factores de crecimiento de los fibroblastos endocrinos (FGF) como el FGF21 regulan el metabolismo al unirse al β-klotho y al FGFR. Este estudio revela la base estructural para la especificidad de FGF21 y la activación de FGFR, ayudando al desarrollo terapéutico.
Área de la Ciencia:
- La bioquímica
- Biología estructural
- Regulación del metabolismo
Sus antecedentes:
- Los factores de crecimiento de fibroblastos canónicos (FGF) se señalan a través de los receptores de FGF (FGFR) con proteoglicanos de sulfato de heparan.
- Los FGFs endocrinos (FGF19, FGF21, FGF23) son hormonas circulantes que regulan el metabolismo y requieren clotos para la señalización de FGFR.
Objetivo del estudio:
- Para aclarar el mecanismo molecular de la especificidad de FGF21 hacia β-klotho.
- Determinar cómo se activa el FGFR de manera dependiente del cloto.
- Proporcionar conocimientos estructurales para el desarrollo de agentes terapéuticos dirigidos a los FGF endocrinos.
Principales métodos:
- Cristalografía de rayos X de las regiones extracelulares β-klotho libres y unidas a los ligandos.
- Análisis estructural de las interacciones FGF21-β-klotho-FGFR.
- Diseño y caracterización de una variante agonista de FGF21.
Principales resultados:
- Las estructuras cristalinas revelan la base molecular de la especificidad de FGF21 para el β-klotho.
- Se ha demostrado un mecanismo de activación del FGFR dependiente del cloto.
- Conocimientos estructurales identificados sobre la evolución de la glucosidasa como receptor de hormonas metabólicas.
- Desarrolló una variante FGF21 con mayor actividad biológica.
Conclusiones:
- El β-Klotho actúa como receptor de orientación primario para el FGF21, con el FGFR como mediador de la señalización intracelular.
- El estudio proporciona una base estructural para la comprensión de la señalización endocrina del FGF en la regulación metabólica.
- Los conocimientos estructurales facilitan el desarrollo de nuevas terapias para las enfermedades metabólicas.
Más Videos Relacionados
Videos de Conceptos Relacionados
02:21Globular and Fibrous Proteins
34.0K
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
34.0K
01:45ER Retrieval Pathway
3.8K
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
3.8K
01:30Assembly of Signaling Complexes
4.7K
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,...
4.7K
01:16TGF - β Signaling Pathway
7.2K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.2K
01:15Activation of Integrins
4.4K
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...
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...
4.4K
01:17Intracellular Signaling Affects Focal Adhesions
2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.8K