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Protein Networks02:26

Protein Networks

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An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
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Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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Overview of Cell Death01:30

Overview of Cell Death

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Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
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The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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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...
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Autophagic Cell Death01:18

Autophagic Cell Death

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Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.3K
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

99
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...
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Updated: Apr 30, 2026

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
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Evaluation of Caspase Activation to Assess Innate Immune Cell Death

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Proteínas de diseño para desencadenar la muerte celular.

Wayne J Fairbrother1, Avi Ashkenazi2

  • 1Department of Early Discovery Biochemistry, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Cell
|June 21, 2014
PubMed
Resumen
Este resumen es generado por máquina.

Los investigadores diseñaron un nuevo inhibidor de polipéptidos utilizando métodos computacionales y evolución dirigida. Este inhibidor se dirige eficazmente a las proteínas virales similares a Bcl-2, induciendo la apoptosis en las células infectadas.

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Área de la Ciencia:

  • La bioquímica es la bioquímica.
  • Biología computacional Biología computacional.
  • Biología Molecular Biología Molecular

Sus antecedentes:

  • El diseño de proteínas de novo se ha limitado históricamente a modificar los andamios de proteínas existentes.
  • El desarrollo de nuevos agentes terapéuticos contra las infecciones virales sigue siendo un desafío crítico.

Objetivo del estudio:

  • Diseñar computacionalmente y validar experimentalmente un inhibidor de polipéptido de novo dirigido a proteínas virales similares al Bcl-2.
  • Para investigar el potencial de este inhibidor en la inducción de la apoptosis de las células infectadas por el virus.

Principales métodos:

  • Utilizó una innovadora estrategia de diseño computacional para crear una nueva estructura de proteínas.
  • Empleado en la evolución dirigida in vitro para optimizar la potencia y la especificidad del inhibidor.
  • Evaluó la eficacia del inhibidor para desencadenar la apoptosis en las células infectadas por el virus.

Principales resultados:

  • Generó con éxito un potente inhibidor de polipéptidos a través del diseño computacional de novo y la evolución dirigida.
  • El inhibidor diseñado demostró una actividad significativa contra una proteína viral similar a la Bcl-2.
  • El inhibidor indujo efectivamente la apoptosis en las células infectadas por el virus, destacando su potencial terapéutico.

Conclusiones:

  • El diseño computacional de novo, cuando se combina con la evolución dirigida, puede producir terapias altamente efectivas basadas en proteínas.
  • El inhibidor polipeptídico desarrollado representa una nueva estrategia prometedora para combatir las infecciones virales mediante la inducción de la muerte celular dirigida.