Engineering cardiolipin binding to an artificial membrane protein reveals determinants for lipid-mediated stabilization

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00619638" target="_blank" >RIV/61388963:_____/25:00619638 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.7554/eLife.104237.3" target="_blank" >https://doi.org/10.7554/eLife.104237.3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.7554/eLife.104237" target="_blank" >10.7554/eLife.104237</a>

Result language

angličtina

Original language name

Engineering cardiolipin binding to an artificial membrane protein reveals determinants for lipid-mediated stabilization

Original language description

Integral membrane proteins carry out essential functions in the cell, and their activities are often modulated by specific protein-lipid interactions in the membrane. Here, we elucidate the intricate role of cardiolipin (CDL), a regulatory lipid, as a stabilizer of membrane proteins and their complexes. Using the in silico-designed model protein TMHC4_R (ROCKET) as a scaffold, we employ a combination of molecular dynamics simulations and native mass spectrometry to explore the protein features that facilitate preferential lipid interactions and mediate stabilization. We find that the spatial arrangement of positively charged residues as well as local conformational flexibility are factors that distinguish stabilizing from non-stabilizing CDL interactions. However, we also find that even in this controlled, artificial system, a clear-cut distinction between binding and stabilization is difficult to attain, revealing that overlapping lipid contacts can partially compensate for the effects of binding site mutations. Extending our insights to naturally occurring proteins, we identify a stabilizing CDL site within the E. coli rhomboid intramembrane protease GlpG and uncover its regulatory influence on enzyme substrate preference. In this work, we establish a framework for engineering functional lipid interactions, paving the way for the design of proteins with membrane-specific properties or functions.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

eLife

ISSN

2050-084X

e-ISSN

2050-084X

Volume of the periodical

14

Issue of the periodical within the volume

April

Country of publishing house

GB - UNITED KINGDOM

Number of pages

21

Pages from-to

RP104237

UT code for WoS article

001479657200001

EID of the result in the Scopus database

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