BID - BH3-interacting domain death agonist | Elisa - Clia - Antibody - Protein

Background

BH3-interacting domain death agonist (BID) is a pro-apoptotic member of the BCL-2 protein family. BID plays a crucial role in the regulation of apoptosis, specifically in the mitochondrial pathway of cell death. It is encoded by the BID gene located on chromosome 22q11.2. BID is unique among the BCL-2 family members due to its ability to interact with both pro-apoptotic and anti-apoptotic proteins, facilitating the apoptotic signaling cascade.

Protein Structure

• Domains: BID consists of a single BH3 (BCL-2 homology 3) domain, which is critical for its pro-apoptotic function. The BH3 domain is essential for BID's interaction with other BCL-2 family proteins.
• Pro- and Active Forms: BID exists in an inactive form in the cytosol. Upon apoptotic stimuli, it is cleaved by caspase-8 to generate the active truncated form, tBID.
• Alpha Helices: The protein's structure predominantly features alpha helices, which facilitate its interaction with the mitochondrial membrane and other BCL-2 family members.

Classification and Subtypes

BID belongs to the "BH3-only" subgroup of the BCL-2 family, characterized by containing only the BH3 domain. This subgroup includes other pro-apoptotic proteins such as BIM, PUMA, and BAD, which initiate apoptosis by antagonizing anti-apoptotic BCL-2 family members and activating pro-apoptotic effectors like BAX and BAK.

Function and Biological Significance

• Apoptosis Activation: BID is a critical mediator of the mitochondrial apoptotic pathway. Upon activation by cleavage, tBID translocates to the mitochondria, where it binds to and activates BAX and BAK. This interaction leads to mitochondrial outer membrane permeabilization (MOMP), cytochrome c release, and the activation of caspases, culminating in cell death.
• Role in Intrinsic and Extrinsic Pathways: BID links the extrinsic (death receptor-mediated) and intrinsic (mitochondrial) apoptotic pathways. Caspase-8, activated by death receptors, cleaves BID, thereby amplifying the apoptotic signal through the mitochondrial pathway.

Clinical Issues

• Cancer: Dysregulation of BID expression or function is implicated in cancer. Reduced BID activity can contribute to resistance to apoptosis, allowing cancer cells to survive and proliferate despite therapeutic interventions.
• Therapeutic Targeting: Modulating BID activity is a potential therapeutic strategy. Enhancing BID activation could sensitize cancer cells to apoptosis, improving the efficacy of anti-cancer therapies.
• Neurodegenerative Diseases: BID-mediated apoptosis is also involved in neurodegenerative diseases. Abnormal activation of BID can lead to excessive neuronal cell death, contributing to diseases such as Alzheimer's and Parkinson's.

Summary

BH3-interacting domain death agonist (BID) is a pivotal pro-apoptotic protein within the BCL-2 family, playing a key role in regulating apoptosis through the mitochondrial pathway. BID is activated by cleavage into tBID, which then promotes mitochondrial membrane permeabilization and cell death. It serves as a crucial link between the extrinsic and intrinsic apoptotic pathways. Dysregulation of BID has significant implications in cancer and neurodegenerative diseases, making it a potential target for therapeutic interventions aimed at modulating apoptosis.