 BH Domains | |
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| Class:Apoptosis | |
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Structure:
The structure of Bcl-XL consist of two central a-helices (a5 (BH1) and a6), which are flanked on one side by a3 and a4 and on the other by a1 (BH4), a2 (BH3) and a7 (BH2). The two central helices contain predominantly hydrophobic residues, and are arranged in an antiparallell fashion. The figure shows the BH1 (yellow), BH2 (magenta), BH3 (orange) and BH4 (cyan) domains of Bcl-XL. The Bak peptide (red), GQAGRQLAIIGDDINR, interacts predominantly with residues in the BH2 and BH3 regions.
Structure Reference: Sattler, M. et al. (1997) Science. 14;275(5302):983-6. PDB: 1BXL.
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Domain binding and function:
Programmed cell death, or apoptosis, is controlled by a number of proteins, among which are members of the widely expressed Bcl-2 family. Bcl-2 Homology (BH) domains are found in all proteins belonging to the Bcl-2 family. There are four BH domains - BH1, BH2, BH3, and BH4. Anti-apoptotic members of the Bcl-2 family, such as Bcl-2, Bcl-xL and Bcl-xW, contain a BH1, BH2 and, in some cases, a BH4 domain. Most pro-apoptotic members of the family, such as Bax and Bak, contain a BH3 domain, though some anti-apoptotic proteins also contain the BH3 domain (Bcl-2 and Bcl-xL). BH domain proteins act as gatekeepers for mitochondrial-induced apoptosis that promote or prevent cytochrome c release into the cytosol and subsequent activation of caspase-9. The BH3 domain promotes dimerization of Bcl-2 family proteins. Homodimerization of Bcl-2 involves a head-to-tail interaction in which the N-terminal region, containing the BH4 domain, interacts with the more distal region of Bcl-2 where BH1, BH2 and BH3 are located. Conversely, Bcl-2/Bax heterodimerization involves a tail-to-tail interaction that requires the BH1, BH2 and BH3 region of Bcl-2 and a central region of Bax containing the BH3 domain.
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Examples of Proteins:
| BH1-BH4 protein |
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Binding partner |
| Bcl-2, Bcl-XL (BH1, BH2, BH3) |  |
Bax, Bad (BH3) |
| Bcl-2 (BH4) | |
Bcl-2 (BH1, BH2, BH3) |
Mcl-1
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Bim, Noxa, PUMA (BH3)
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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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