8srx

Crystal structure of BAK-BAX heterodimer with lysoPCCrystal structure of BAK-BAX heterodimer with lysoPC

Structural highlights

8srx is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.09Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BAK_HUMAN In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis.^[1] ^[2]

Publication Abstract from PubMed

The B-cell lymphoma 2 (BCL2) family members, BCL2-associated protein X (BAX) and BCL2 homologous antagonist killer (BAK), are required for programmed cell death via the mitochondrial pathway. When cells are stressed, damaged or redundant, the balance of power between the BCL2 family of proteins shifts towards BAX and BAK, allowing their transition from an inactive, monomeric state to a membrane-active oligomeric form that releases cytochrome c from the mitochondrial intermembrane space. That oligomeric state has an essential intermediate, a symmetric homodimer of BAX or BAK. Here we describe crystal structures of dimers of the core domain of BAX, comprising its helices alpha2-alpha5. These structures provide an atomic resolution description of the interactions that drive BAX homo-dimerisation and insights into potential interaction between core domain dimers and membrane lipids. The previously identified BAK lipid-interacting sites are not conserved with BAX and are likely to determine the differences between them in their interactions with lipids. We also describe structures of heterodimers of BAK/BAX core domains, yielding further insight into the differences in lipid binding between BAX and BAK.

Sequence differences between BAX and BAK core domains manifest as differences in their interactions with lipids.,Miller MS, Cowan AD, Brouwer JM, Smyth ST, Peng L, Wardak AZ, Uren RT, Luo C, Roy MJ, Shah S, Tan Z, Reid GE, Colman PM, Czabotar PE FEBS J. 2023 Dec 13. doi: 10.1111/febs.17031. PMID:38088212^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Chittenden T, Flemington C, Houghton AB, Ebb RG, Gallo GJ, Elangovan B, Chinnadurai G, Lutz RJ. A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. EMBO J. 1995 Nov 15;14(22):5589-96. PMID:8521816
↑ Moldoveanu T, Liu Q, Tocilj A, Watson M, Shore G, Gehring K. The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site. Mol Cell. 2006 Dec 8;24(5):677-88. PMID:17157251 doi:10.1016/j.molcel.2006.10.014
↑ Miller MS, Cowan AD, Brouwer JM, Smyth ST, Peng L, Wardak AZ, Uren RT, Luo C, Roy MJ, Shah S, Tan Z, Reid GE, Colman PM, Czabotar PE. Sequence differences between BAX and BAK core domains manifest as differences in their interactions with lipids. FEBS J. 2023 Dec 13. PMID:38088212 doi:10.1111/febs.17031

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OCA

[1] Chittenden T, Flemington C, Houghton AB, Ebb RG, Gallo GJ, Elangovan B, Chinnadurai G, Lutz RJ. A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions. EMBO J. 1995 Nov 15;14(22):5589-96. PMID:8521816

[2] Moldoveanu T, Liu Q, Tocilj A, Watson M, Shore G, Gehring K. The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site. Mol Cell. 2006 Dec 8;24(5):677-88. PMID:17157251 doi:10.1016/j.molcel.2006.10.014

[3] Miller MS, Cowan AD, Brouwer JM, Smyth ST, Peng L, Wardak AZ, Uren RT, Luo C, Roy MJ, Shah S, Tan Z, Reid GE, Colman PM, Czabotar PE. Sequence differences between BAX and BAK core domains manifest as differences in their interactions with lipids. FEBS J. 2023 Dec 13. PMID:38088212 doi:10.1111/febs.17031

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