Zamora Carreras, HéctorMaestro García-Donas, María BeatrizStrandberg, EricUlrich, AnneSanz, JesúsJiménez, María Ángeles2024-01-312024-01-312018Zamora‐Carreras, Héctor, et al. «Roles of Amphipathicity and Hydrophobicity in the Micelle‐Driven Structural Switch of a 14‐mer Peptide Core from a Choline‐Binding Repeat». Chemistry – A European Journal, vol. 24, n.o 22, abril de 2018, pp. 5825-39. https://doi.org/10.1002/chem.201704802.0947-653910.1002/chem.201704802https://hdl.handle.net/20.500.14352/96984This work was supported by the Spanish MINECO grants (co-financed by European FEDER funds): CTQ2017-84371-P, CTQ2014-52633-P, BIO2016-79323-R and BIO2013-47684-R; and by the German Helmholtz Gemeinschaft. H. Zamora-Carreras was a recipient of a FPI scholarship (BES-2012-057717), and his stay at KIT, Germany was financed by the Spanish MINECO short stay grant EEBB-I-14-08805.Choline-binding repeats (CBRs) are ubiquitous sequences with a β-hairpin core that are found in the surface proteins of several microorganisms such as S. pneumoniae (pneumococcus). Previous studies on a 14-mer CBR sequence derived from the pneumoccal LytA autolysin (LytA239–252 peptide) have demonstrated a switch behaviour for this peptide, so that it acquires a stable, native-like β-hairpin conformation in aqueous solution but is reversibly transformed into an amphipathic α-helix in the presence of detergent micelles. With the aim of understanding the factors responsible for this unusual β-hairpin to α-helix transition, and to specifically assess the role of peptide hydrophobicity and helical amphipathicity in the process, we designed a series of LytA239–252 variants affecting these two parameters and studied their interaction with dodecylphosphocholine (DPC) micelles by solution NMR, circular dichroism and fluorescence spectroscopies. Our results indicate that stabilising cross-strand interactions become essential for β-hairpin stability in the absence of optimal turn sequences. Moreover, both amphipathicity and hydrophobicity display comparable importance for helix stabilisation of CBR-derived peptides in micelles, indicating that these sequences represent a novel class of micelle/membrane-interacting peptides.engjournal articlehttps://doi.org/10.1002/chem.201704802restricted access577.112MicellesPeptidesProtein foldingProtein structuresStructural biologyBioquímica (Química)2403 Bioquímica2302.18 Lípidos