Dysregulated interactions triggered by a neuropathy-causing mutation in the IPV motif of HSP27

Abstract

Molecular chaperone | small heat-shock protein | Charcot-Marie-Tooth disease | short linear motif | nuclear magnetic resonance | protein aggregation | neurological diseaseCorrespondence: vincent.timmerman@uantwerpen.be, andrew.baldwin@chem.ox.ac.uk, justin.benesch@chem.ox.ac.uk the backbone atoms of V111, T113, and L157 (Fig. 1E). In HSP27, the IxI/V motif corresponds to I181-P182-V183; the Ile and Val residues penetrate the β4/β8 groove while P182 does not make any direct contacts with the ACD (Fig. 1E).The P182L variant has impaired chaperone activity in vitro. We purified recombinant human HSP27 and the CMTimplicated P182L variant from E. coli, and compared their chaperone activities in vitro using a substrate aggregation assay. We tested their ability to prevent the aggregation of two model substrate proteins, malate dehydrogenase (MDH) and

Reductive Stress-Induced Mitochondrial Dysfunction and Cardiomyopathy

“…However, other studies showed that overexpression of Hsp27 could protect myocardium during ischemic stress [95,[99][100][101]. Therefore, Hsp27, with its potent antiaggregation activity [102], may serve as an important indicator of the risk assessment and prevention of developing heart lesion as well as a target for cardiomyopathy treatment [103,104]. Further studies are needed to clarify if increased Hsp27 is actually beneficial and is in response to stress exposure [105].…”

Decoding and influencing mitochondrial inner membrane ultra-structure biogenesis

“…Interestingly, the AxA motifs can also enhance oligomeric interaction within protein molecules as shown previously by other studies (Alderson et al, 2019;Studer et al, 2002). Therefore, it would be important to further mutate these GxGxG motifs by replacing glycine residues with leucine residues to observe their exact effects on the overall oligomerization pattern of Mic10 as was…”