WW domains are present in many signaling proteins and, due to their compact fold and small size, have become models for folding studies. With the group of Dr. H. Scheraga, we have investigated the folding kinetics of WW domains and mutants. In this case, we combined the information obtained by NMR of eight WW point mutations, together with the coarse-grained united-residue (UNRES) force field developed in Scheraga’s group. With this multidisciplinary approach, we were able to predict the folding kinetics trajectories of these mutants and bridge theoretical and experimental worlds. We also characterized some folding intermediates, which were associated with formation of amyloid fibrils, present in a number of neurodegenerative disorders (PNAS 2015).

We have also studied the mechanism of the cytoplasmic polyadenylation element binding protein (CPEB) degradation, with the peptidyl-prolyl cis/trans isomerase Pin1 being identified as a crucial factor regulating this process. Pin1 is bound to CPEB1 prior to its phosphorylation and the interaction gains affinity when CPEB1 is phosphorylated. Pin1 binding sites are located close to the E3 ubiquitin ligase SCFβ−TrCP site, explaining the role of Pin1 in CPEB degradation (Scientific reports 2015).

Relevant publications:

1. Maisuradze G.G., Medina J., Kachlishvili K., Krupa P., Mozolewska M.A., Martin-Malpartida P., Maisuradze L., Macias M.J.* and Scheraga H.A. * Preventing fibril formation of a protein by selective mutation. Proc. Natl. Acad. Sci. USA, 112(44): 13549-54, 2015.
2. Schelhorn C., Martín-Malpartida P., Suñol D., and Macias M.J.* Structural Analysis of the Pin1-CPEB1 interaction and its potential role in CPEB1 degradation. Scientific Reports, 5, 14990, 2015.