Mortalin's machinery

• Main Authors: Deocaris, Custer C., Kaul, Sunil C., Wadhwa, Renu
• Format: text
• Published: Animo Repository 2012
• Subjects: Tumor suppressor proteins; Molecular chaperones; Protein binding; Cancer Biology
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/5457
• Institution: De La Salle University

Mortalin/mtHsp70 performs a wide array of cellular functions and has been implicated in aging, cancer and neurodegenerative diseases. Similar to other Hsp70s, its ability to chaperone misfolded proteins and bind to a myriad of clients is derived from its N-terminal nucleotide-binding domain (NBD) regulating substrate affinity of the C-terminal substrate-binding domain (SBD) in a nucleotide- and co-chaperone-dependent mechanism. To understand the structural dynamics of its allostery making this relevant to mortalin’s cellular function, this chapter describes key structural features of these two domains as well as provide an appreciation as to possibly how a single amino acid change, Gly to Arg in the SBD that can be viewed so minor, is able to metamorphose from a life-extending species of mortalin (mot-2) into one that induces senescence and even inhibits tumor growth (mot-1).