Effect of UV Stress on the Structure and Function of Pro‐apoptotic Bid and Anti‐apoptotic Bcl‐xl proteins. (3rd February 2023)

• Record Type: Journal Article
• Authors: Bera, Akash; Singh, Suraj; D'Souza, Jacinta S.; Hosur, Ramakrishna V.; Mishra, Pushpa
• Is Part Of: Chembiochem. Volume 24:Number 5(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-02-03
• Subjects: apoptosis -- Bid -- Bcl-xl -- NMR spectroscopy -- UV-C; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202200682
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Ultraviolet C (UV‐C) radiation induces apoptosis in mammalian cells via the mitochondrion‐mediated pathway. The Bcl‐2 family of proteins are the regulators of the mitochondrial pathway of apoptosis and appears responsive to UV‐C radiation. It is unknown how the structure and, effectively, the function of these proteins are directly impacted by UV‐C exposure. Here, we present the effect of UV‐C irradiation on the structure and function of pro‐apoptotic Bid‐FL and anti‐apoptotic Bcl‐xlΔC proteins. Using a variety of biophysical tools, we show that, following UV‐C irradiation, the structures of Bcl‐xlΔC and Bid‐FL are irreversibly altered. Bcl‐xLΔC is found to be more sensitive to UV stress than Bid‐FL Interestingly, UV‐C exposure shows dramatic chemical shift perturbations in consequence of dramatic structural perturbations (α‐helix to β‐sheet) in the BH3‐ binding region, a crucial segment of Bcl‐xlΔC. Furter it has been shown that UV‐exposed Bcl‐xlΔC has reduced efficacy of its interactions with pro‐apoptotic tBid. Abstract : UV on, apoptosis on : Bcl‐xl anti‐apoptotic protein binds to pro‐apoptotic protein Bid in the BH3 binding region. Pro‐apoptotic protein initiates apoptosis by activating Bax. Bcl‐xl sequesters initiator proteins and does not let Bax activation occur; this results in no apoptosis. It has been observed upon UV exposure, Bcl‐xl binding to pro‐apoptotic protein diminishes, which in‐turn liberates free tBid in solution resulting in apoptosis.