S-nitrosylation affects TRAP1 structure and ATPase activity and modulates cell response to apoptotic stimuli.

S-nitrosylation affects TRAP1 structure and ATPase activity and modulates cell response to apoptotic stimuli. Biochem Pharmacol. 2020 Feb 20;:113869 Authors: Faienza F, Lambrughi M, Rizza S, Pecorari C, Giglio P, Salamanca Viloria J, Francesca Allega M, Chiappetta G, Vinh J, Pacello F, Battistoni A, Rasola A, Papaleo E, Filomeni G Abstract The mitochondrial chaperone TRAP1 has been involved in several mitochondrial functions, and modulation of its expression/activity has been suggested to play a role in the metabolic reprogramming distinctive of cancer cells. TRAP1 posttranslational modifications, i.e. phosphorylation, can modify its capability to bind to different client proteins and modulate its oncogenic activity. Recently, it has been also demonstrated that TRAP1 is S-nitrosylated at Cys501, a redox modification associated with its degradation via the proteasome. Here we report molecular dynamics simulations of TRAP1, together with analysis of long-range structural communication, providing a model according to which Cys501 S-nitrosylation induces conformational changes to distal sites in the structure of the protein. The modification is also predicted to alter open and closing motions for the chaperone function. By means of colorimetric assays and site directed mutagenesis aimed at generating C501S variant, we also experimentally confirmed that selective S-nitrosylation of Cys501 decreases ATPase activity of recombinant TRAP1. Co...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research