Video Experimental Relacionado
Updated: May 2, 2026
06:51
Studies of Chaperone-Cochaperone Interactions using Homogenous Bead-Based Assay
Published on: July 21, 2021
2.1K
El complejo Hsp90-Tau revela la base molecular para la especificidad en la acción de la chaperona
G Elif Karagöz1, Afonso M S Duarte2, Elias Akoury3
1Cellular Protein Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands; Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.
Cell
|March 4, 2014
Resumen
Las chaperones moleculares Proteína de choque térmico 70 (Hsp70) y Proteína de choque térmico 90 (Hsp90) manejan el plegamiento de las proteínas. Un nuevo modelo revela cómo Hsp90 reconoce intermediarios de plegado en etapa tardía y proteínas intrínsecamente desordenadas como Tau.
Área de la Ciencia:
- Biología molecular La biología molecular.
- Biología estructural Biología estructural.
- La bioquímica es la bioquímica.
Sus antecedentes:
- El plegamiento de las proteínas celulares está regulado por los sistemas de chaperona molecular, principalmente Hsp70 y Hsp90.
- Hsp70 actúa temprano, mientras que Hsp90 actúa más tarde en la vía de plegamiento de la proteína.
- La especificidad del sustrato y el mecanismo preciso de sincronización de Hsp90 siguen siendo poco conocidos.
Objetivo del estudio:
- Para dilucidar la base molecular de la especificidad del sustrato Hsp90.
- Para entender cómo Hsp90 distingue los intermediarios de plegado tardío de los primeros.
- Para modelar la interacción entre Hsp90 y su sustrato asociado a la enfermedad, la proteína Tau.
Principales métodos:
- Generación de un modelo estructural del complejo Hsp90-Tau.
- Análisis de la interfaz de unión al sustrato Hsp90.
- Investigación del mecanismo de reconocimiento de Hsp90 para los residuos hidrofóbicos.
Principales resultados:
- Hsp90 se une ampliamente a la proteína Tau, incluidas las regiones propensas a la agregación.
- Una gran interfaz de unión Hsp90 (106 Å) facilita numerosos contactos de baja afinidad.
- Hsp90 reconoce residuos hidrofóbicos dispersos en intermedios de plegado tardío, distintos de los sitios de unión de Hsp70.
Conclusiones:
- El amplio mecanismo de unión de baja afinidad de Hsp90 explica su especificidad para los intermediarios de plegado tardío.
- Este mecanismo también explica la capacidad de Hsp90 para unirse a proteínas intrínsecamente desordenadas.
- El modelo estructural proporciona información sobre la coordinación funcional entre los sistemas de chaperón Hsp70 y Hsp90.
Videos de Conceptos Relacionados
03:00Molecular Chaperones and Protein Folding
14.7K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
14.7K
03:00Molecular Chaperones and Protein Folding
14.2K
14.2K
02:41Protein Complex Assembly
12.5K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
12.5K
01:26Bacterial Protein Maturation
744
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
744
01:45Tail-anchoring of Proteins in the ER Membrane
2.8K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
2.8K
01:37Energy to Drive Translocation
2.0K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.0K