Inverse Conformational Selection in Lipid-Protein Binding
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F21%3A00545666" target="_blank" >RIV/61388963:_____/21:00545666 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1021/jacs.1c05549" target="_blank" >https://doi.org/10.1021/jacs.1c05549</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/jacs.1c05549" target="_blank" >10.1021/jacs.1c05549</a>
Alternative languages
Result language
angličtina
Original language name
Inverse Conformational Selection in Lipid-Protein Binding
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10403 - Physical chemistry
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of the American Chemical Society
ISSN
0002-7863
e-ISSN
1520-5126
Volume of the periodical
143
Issue of the periodical within the volume
34
Country of publishing house
US - UNITED STATES
Number of pages
9
Pages from-to
13701-13709
UT code for WoS article
000704514200028
EID of the result in the Scopus database
2-s2.0-85114164673