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bioRxiv · 10.1101/2025.06.16.659449

Monomeric and oligomeric forms of Bcl-xL in direct andindirect inhibition of apoptosis

Elsner, C.·Roderer, D.·Bordignon, E.
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Abstract

The Bcl-2 protein Bcl-xL is an inhibitor of intrinsic apoptosis which either directly inhibits the pore-forming Bcl-2 proteins, like Bax or Bak, or indirectly inhibits pore formation by sequestering the pro-apoptotic BH3-only activators. The structural basis of the inhibition of pore formation in the outer mitochondrial membrane is still largely unknown due to the lack of atomic resolution structures of the relevant inhibitory complexes at the membrane. Here we present a protocol to obtain high-yield recombinant monomeric full-length Bcl-xL proteins. The monomeric Bcl-xL retains the ability to shuttle between membrane and aqueous environments and can successfully inhibit Bcl-2-induced membrane permeabilization via both modes of action, as proven by in vitro and in organelle assays with a minimal Bcl-2 interactome constituted by Bcl-xL, cBid, and Bax.

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Elsner, C., Roderer, D., Bordignon, E.. 2025-06-20. Monomeric and oligomeric forms of Bcl-xL in direct andindirect inhibition of apoptosis. https://doi.org/10.1101/2025.06.16.659449

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