Inverse Conformational Selection in Lipid-Protein Binding

0545666 - ÚOCHB 2022 RIV US eng J - Článek v odborném periodiku
Bacle, A. - Buslaev, P. - Garcia-Fandino, R. - Favela-Rosales, F. - Mendes Ferreira, T. - Fuchs, P. F. J. - Gushchin, I. - Javanainen, Matti - Kiirikki, A. M. - Madsen, J. J. - Melcr, J. - Milán Rodríguez, P. - Miettinen, M. S. - Ollila, O. H. S. - Papadopoulos, C. G. - Peón, A. - Piggot, T. J. - Piñeiro, Á. - Virtanen, S.
Inverse Conformational Selection in Lipid-Protein Binding.
Journal of the American Chemical Society. Roč. 143, č. 34 (2021), s. 13701-13709. ISSN 0002-7863. E-ISSN 1520-5126
Institucionální podpora: RVO:61388963
Klíčová slova: membrane lipids * phosphatidylcholine headgroup * phospholipid binding
Obor OECD: Physical chemistry
Impakt faktor: 16.383, rok: 2021
Způsob publikování: Open access
https://doi.org/10.1021/jacs.1c05549

Interest in lipid interactions with proteins and other biomolecules is emerging not only in fundamental biochemistry but also in the field of nanobiotechnology where lipids are commonly used, for example, in carriers of mRNA vaccines. The outward-facing components of cellular membranes and lipid nanoparticles, the lipid headgroups, regulate membrane interactions with approaching substances, such as proteins, drugs, RNA, or viruses. Because lipid headgroup conformational ensembles have not been experimentally determined in physiologically relevant conditions, an essential question about their interactions with other biomolecules remains unanswered: Do headgroups exchange between a few rigid structures, or fluctuate freely across a practically continuous spectrum of conformations? Here, we combine solid-state NMR experiments and molecular dynamics simulations from the NMRlipids Project to resolve the conformational ensembles of headgroups of four key lipid types in various biologically relevant conditions. We find that lipid headgroups sample a wide range of overlapping conformations in both neutral and charged cellular membranes, and that differences in the headgroup chemistry manifest only in probability distributions of conformations. Furthermore, the analysis of 894 protein-bound lipid structures from the Protein Data Bank suggests that lipids can bind to proteins in a wide range of conformations, which are not limited by the headgroup chemistry. We propose that lipids can select a suitable headgroup conformation from the wide range available to them to fit the various binding sites in proteins. The proposed inverse conformational selection model will extend also to lipid binding to targets other than proteins, such as drugs, RNA, and viruses.
Trvalý link: http://hdl.handle.net/11104/0322335


Vědecká data: Zenodo