1 research outputs found
NMR Solution Structure of a Photoswitchable Apoptosis Activating Bak Peptide Bound to Bcl-x<sub>L</sub>
The Bcl-2 family of proteins includes the major regulators
and
effectors of the intrinsic apoptosis pathway. Cancers are frequently
formed when activation of the apoptosis mechanism is compromised either
by misregulated expression of prosurvival family members or, more
frequently, by damage to the regulatory pathways that trigger intrinsic
apoptosis. Short peptides derived from the pro-apoptotic members of
the Bcl-2 family can activate mechanisms that ultimately lead to cell
death. The recent development of photocontrolled peptides that are
able to change their conformation and activity upon irradiation with
an external light source has provided new tools to target cells for
apoptosis induction with temporal and spatial control. Here, we report
the first NMR solution structure of a photoswitchable peptide derived
from the proapoptotic protein Bak in complex with the antiapoptotic
protein Bcl-x<sub>L</sub>. This structure provides insight into the
molecular mechanism, by which the increased affinity of such photopeptides
compared to their native forms is achieved, and offers a rationale
for the large differences in the binding affinities between the helical
and nonhelical states