Related Experiment Video

Updated: Aug 14, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis

M Sattler1, H Liang, D Nettesheim

  • 1Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064, USA.

Science (New York, N.Y.)
|February 14, 1997
PubMed

Insights

Understanding programmed cell death requires studying protein interactions. This research reveals how the Bcl-xL survival protein binds to the Bak protein, crucial for cell death regulation.

Area of Science:

  • Molecular Biology
  • Cell Death Regulation
  • Protein Structure and Interactions

Background:

  • Heterodimerization among Bcl-2 family proteins is critical for controlling programmed cell death.
  • Understanding these protein-protein interactions at a molecular level is essential for deciphering cell death pathways.

Purpose of the Study:

  • To investigate the molecular basis of heterodimer formation between Bcl-xL and Bak.
  • To elucidate the structural interactions governing the complex between the survival protein Bcl-xL and the death-promoting protein Bak.

Main Methods:

  • Solution structure determination of the Bcl-xL/Bak complex.
  • Analysis of binding affinities using mutant Bak peptides.
  • Investigating the role of hydrophobic and electrostatic interactions in complex formation.

Main Results:

  • The Bak peptide forms an amphipathic alpha helix upon binding to Bcl-xL.
  • Interactions involve both hydrophobic and electrostatic forces between Bak and Bcl-xL.
  • Mutations disrupting these interactions in Bak prevent heterodimerization with Bcl-xL.

Conclusions:

  • The study elucidates the structural basis for Bcl-xL and Bak heterodimerization.
  • Both hydrophobic and electrostatic interactions are vital for the functional binding of Bak to Bcl-xL.
  • These findings provide insights into the regulation of programmed cell death by Bcl-2 family proteins.

More Related Videos

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling08:51

Applying an Inducible Expression System to Study Interference of Bacterial Virulence Factors with Intracellular Signaling

Published on: June 25, 2015

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

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...
Caspases01:24

Caspases

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.
The Extrinsic Apoptotic Pathway01:17

The 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...
The Intrinsic Apoptotic Pathway01:31

The 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...
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

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,...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular 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...