“Micelle-triggered chameleonic behaviour in peptides derived from pneumococcal LytA autolysin”
Héctor Zamora Carreras
Miércoles 11 de marzo
Salón de actos, 12:00
“Micelle-triggered chameleonic behaviour in peptides derived from pneumococcal LytA autolysin”
Héctor Zamora Carreras
Miércoles 11 de marzo
Salón de actos, 12:00
LytA autolysin from S. pneumoniae belongs to the choline-binding proteins (CBP) family. CBPs present a modular structure including a choline-binding module (CBM) composed of choline-binding repeats (CBRs). In the case of LytA, its CBM consists of six repeats, each one of which contains a 14-residue β -hairpin followed for a 6-residue linker sequence, with the choline molecules bound between two consecutive repeats. As the CBMs possess interesting biotechnological applicability and they are good models to understand folding and stability of repeat proteins, we aim to find whether minimal peptides encompassing the sequence of a single CBR or even only its β -hairpin core maintain the ability to bind choline. The promising previous studies on peptide CLyt1 (derived from CBR1 from LytA) led us to select a new peptide candidate: CLyt3, derived from CBR3. CD and NMR data demonstrate that CLyt3 forms a highly stable native-like β-hairpin both in aqueous solution and in the presence of TFE but strikingly the peptide structure is a stable amphipathic α-helix in different detergent micelles (DPC and SDS). We found that this β -hairpin-to- α -helix transition is reversible. Considering our findings, we have proposed amphipathicity as a requirement for a peptide to interact and to be stable in micellar media. We have also observed a similar behaviour in peptides derived from other CBRs from LytA (CLyt4 and CLyt34) and, to our knowledge, this "chameleonic" behaviour is the only described case of a micelle-induced structural transition between two ordered peptide structures. We consider these results could not only be of relevance in the field of peptide design and biosensors, but also may help to understand the molecular basis for the peculiar mechanism of LytA translocation from the cytoplasm to the bacterial surface.