Does a Similar 3D Structure Mean a Similar Folding Pathway? The Presence of a C-Terminal α-Helical Extension in the 3D Structure of MAX60 Drastically Changes the Folding Pathway Described for Other MAX-Effectors from Magnaporthe oryzae

Does a similar 3D structure mean a similar folding pathway? This question is particularly meaningful when it concerns proteins sharing a similar 3D structure, but low sequence identity or homology. MAX effectors secreted by the phytopathogenic fungus Magnaporthe oryzae present such characteristics. They share a common 3D structure, a ß-sandwich with the same topology for all the family members, but an extremely low sequence identity/homology. In a previous study, we have investigated the folding of two MAX effectors, AVR-Pia and AVR-Pib, using High-Hydrostatic-Pressure NMR and found that they display a similar folding pathway, with a common folding intermediate. In the present work, we used a similar strategy to investigate the folding conformational landscape of another MAX effector, MAX60, and found a very different folding intermediate. Our analysis strongly supports that the presence of a C-terminal $\mathsf{\alpha }$-helical extension in the 3D structure of MAX60 could be responsible for its different folding pathway.