pH-Induced Folding of the Caspase-Cleaved Par-4 Tumor Suppressor: Evidence of Structure Outside of the Coiled Coil Domain

Biomolecules

EmilyM. Raitt¹  AndreaM. Clark¹  MeghanS. Warden¹  AndreaC. Yawn¹  StevenM. Pascal¹  Komala Ponniah¹ 

[1] Department of Chemistry and Biochemistry, Old Dominion University, Norfolk, VA 23529, USA;

关键词: prostate apoptosis response-4 (Par-4);    intrinsically disordered protein (IDP);    cancer;    circular dichroism;    coiled coil (CC), leucine zipper (LZ), apoptosis;   

DOI  :  10.3390/biom8040162

来源: DOAJ

【 摘 要 】

Prostate apoptosis response-4 (Par-4) is a 38 kDa largely intrinsically disordered tumor suppressor protein that functions in cancer cell apoptosis. Par-4 down-regulation is often observed in cancer while up-regulation is characteristic of neurodegenerative conditions such as Alzheimer’s disease. Cleavage of Par-4 by caspase-3 activates tumor suppression via formation of an approximately 25 kDa fragment (cl-Par-4) that enters the nucleus and inhibits Bcl-2 and NF-ƙB, which function in pro-survival pathways. Here, we have investigated the structure of cl-Par-4 using biophysical techniques including circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and intrinsic tyrosine fluorescence. The results demonstrate pH-dependent folding of cl-Par-4, with high disorder and aggregation at neutral pH, but a largely folded, non-aggregated conformation at acidic pH.

【 授权许可】

Unknown