BH domain binding

Definition

Target type: molecularfunction

Binding to a Bcl-2 homology (BH) protein domain. Bcl-2-related proteins share homology in one to four conserved regions designated the Bcl-2 homology (BH) domains BH1, BH2, BH3 and BH4. These domains contribute at multiple levels to the function of these proteins in cell death and survival. Anti-apoptotic members of the Bcl-2 family have four BH domains (BH1-BH4). Pro-apoptotic members have fewer BH domains. [PMID:11048732, PMID:12133724, PMID:9020082, PMID:9704409]

BH domain binding is a molecular interaction that plays a critical role in regulating apoptosis, a programmed cell death process essential for development and homeostasis. BH domains are conserved protein domains found in a variety of proteins involved in apoptosis, particularly members of the Bcl-2 family. These domains are characterized by their alpha-helical structure and typically consist of around 70 amino acids.

The BH domain binding process involves the interaction between BH domains on different proteins, leading to the formation of multi-protein complexes. These complexes can either promote or inhibit apoptosis, depending on the specific proteins involved.

**Pro-apoptotic BH domain binding:**

* **BH3-only proteins:** These proteins contain only a single BH3 domain and are typically activated in response to apoptotic stimuli. Upon activation, they bind to the BH3 binding groove of pro-survival proteins, such as Bcl-2, Bcl-xL, and Mcl-1, thereby inhibiting their anti-apoptotic activity.
* **Bax and Bak:** These proteins contain multiple BH domains, including a BH3 domain. Upon activation, they oligomerize and insert into the mitochondrial membrane, forming pores that allow the release of cytochrome c and other apoptotic factors into the cytosol.

**Anti-apoptotic BH domain binding:**

* **Pro-survival proteins:** These proteins, such as Bcl-2, Bcl-xL, and Mcl-1, contain multiple BH domains, including a BH3 binding groove. They bind to BH3-only proteins, preventing their activation and inhibiting the apoptotic cascade.

**Regulation of BH domain binding:**

The interaction between BH domains is tightly regulated by various mechanisms, including:

* **Post-translational modifications:** Phosphorylation, acetylation, and ubiquitination of BH domain proteins can influence their activity and interactions.
* **Conformational changes:** The conformation of BH domains can be altered by binding to other proteins or by changes in cellular conditions, such as stress or DNA damage.
* **Cellular localization:** The localization of BH domain proteins within the cell can affect their accessibility and interaction with other proteins.

**Overall, BH domain binding is a highly regulated process that plays a crucial role in the apoptotic cascade. Understanding the molecular mechanisms of BH domain binding is essential for developing new therapeutic strategies for cancer and other diseases involving abnormal cell death.'
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Proteins (8)

Compounds (70)