Peptide LIQ promotes cell protection against zinc-induced cytotoxicity through microtubule stabilization

Stability of microtubule protein (MTP) network required for its physiological functions is disrupted in the course of neurodegenerative disorders. Thus, design of novel therapeutic approaches for microtubule stabilization is a focus of intensive study. Dynamin-related protein-1 (Drp1) is a guanosine triphosphatase (GTPase), which plays a prevailing role in mitochondrial fission. Several isoforms of Drp1 have been identified that one of these isoforms (Drp1-x01) has been previously described with MTP stabilizing activity. Here, we synthesized peptide LIQ, an 11-amino acid peptide derived from Drp1-x01 isoform, and reported that LIQ could induce tubulin assembly in vitro. Using Stern-Volmer plot and continuous variation method, we proposed one binding site on tubulin for this peptide. Interestingly, FRET experiment and docking studies showed that LIQ binds taxol-binding site on β-tubulin. Furthermore, circular dichroism (CD) spectroscopy and 8-anilino-1-naphthalenesulfonic acid (ANS) assay provided data on ...