Video Experimental Relacionado
Updated: May 17, 2026
07:42
Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
La protonación de His26 en el citocromo c desencadena en un microsegundo la formación de láminas β y la exposición al
Gurusamy Balakrishnan1, Ying Hu, Thomas G Spiro
1Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA.
Journal of the American Chemical Society
|October 26, 2012
Resumen
El citocromo c se despliega de manera reversible en una estructura de hoja beta, interrumpiendo su enlace hemo y ganando actividad peroxidasa. Este proceso implica eventos específicos de protonación y puede estar relacionado con la peroxidación de cardiolipina vinculada a la apoptosis.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Dinámica de las proteínas Dinámica de las proteínas
- La espectroscopia es una técnica de espectroscopia.
Sus antecedentes:
- El citocromo c (cyt c) es una proteína clave en la apoptosis.
- Su actividad peroxidasa está relacionada con la peroxidación de la cardiolipina.
- Comprender el desarrollo de las células es crucial para sus funciones biológicas.
Objetivo del estudio:
- Investigar el mecanismo del despliegue del citocromo c a pH bajo.
- Caracterizar los cambios estructurales y su correlación con las alteraciones funcionales.
- Para aclarar el papel de residuos específicos y elementos estructurales en el proceso de despliegue.
Principales métodos:
- Espectroscopia de resonancia UV Raman (UVRR) para sondear la estructura secundaria.
- Salto de temperatura (salto en T) junto con UVRR para mediciones con resolución temporal.
- Análisis de las interacciones de residuos aromáticos y propionato de hemo.
Principales resultados:
- El calentamiento a pH 3 induce el despliegue local y reversible de la citocina.
- El despliegue convierte giros y hélices en estructuras de hojas beta, no en bobinas aleatorias.
- La ruptura del enlace Met80-hemo y la orientación alterada de los residuos aromáticos indican un desplazamiento del hemo.
- La protonación de His26 interrumpe su interacción con Pro44, iniciando una cascada de despliegue.
- Se determinaron las constantes de tiempo para la formación de hojas beta y la reorientación de Trp59 (0.2, 3.9, 67 μs).
Conclusiones:
- El mecanismo de despliegue implica protonación específica y cambios en la estructura secundaria, lo que lleva a la exposición al hemo y la actividad de la peroxidasa.
- Este mecanismo puede ser relevante para la peroxidación de la cardiolipina mediada por citocinas durante la apoptosis.
- El bucle 40s Ω, anclado por la interacción His26-Pro44, actúa como un "doblado" crítico en el despliegue de la célula.
Videos de Conceptos Relacionados
01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:46Electron Transport Chain: Complex I and II
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
01:22Cellular Injury V: Apoptosis and Autophagy
Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
03:00Molecular Chaperones and Protein Folding
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...