Home > Documents in Process > Physics-based evolution of transmembrane helices reveals mechanisms of cholesterol attraction. > print

001     281795
005     20251021124955.0
024 7 _ |a 10.1038/s41467-025-63769-5
|2 doi
024 7 _ |a pmid:41115860
|2 pmid
037 _ _ |a DZNE-2025-01185
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Methorst, Jeroen
|0 0000-0003-4507-4882
|b 0
245 _ _ |a Physics-based evolution of transmembrane helices reveals mechanisms of cholesterol attraction.
260 _ _ |a [London]
|c 2025
|b Springer Nature
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1761043655_16841
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a The existence of linear cholesterol-recognition motifs in transmembrane domains has long been debated. Evolutionary molecular dynamics (Evo-MD) simulations-genetic algorithms guided by (coarse-grained) molecular force-fields-reveal that thermodynamic optimal cholesterol attraction in isolated alpha-helical transmembrane domains occurs when multiple consecutive lysine/arginine residues flank a short hydrophobic segment. These findings are supported by atomistic simulations and solid-state NMR experiments. Our analyses illustrate that linear motifs in transmembrane domains exhibit weak binding affinity for cholesterol, characterized by sub-microsecond residence times, challenging the predictive value of linear CRAC/CARC motifs for cholesterol binding. Membrane protein database analyses suggest even weaker affinity for native linear motifs, whereas live cell assays demonstrate that optimizing cholesterol binding restricts transmembrane domains to the endoplasmic reticulum post-translationally. In summary, these findings contribute to our understanding of cholesterol-protein interactions and offer insight into the mechanisms of protein-mediated cholesterol regulation within membranes.
536 _ _ |a 351 - Brain Function (POF4-351)
|0 G:(DE-HGF)POF4-351
|c POF4-351
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a Cholesterol
|0 97C5T2UQ7J
|2 NLM Chemicals
650 _ 7 |a Membrane Proteins
|2 NLM Chemicals
650 _ 2 |a Cholesterol: metabolism
|2 MeSH
650 _ 2 |a Cholesterol: chemistry
|2 MeSH
650 _ 2 |a Molecular Dynamics Simulation
|2 MeSH
650 _ 2 |a Membrane Proteins: chemistry
|2 MeSH
650 _ 2 |a Membrane Proteins: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Thermodynamics
|2 MeSH
650 _ 2 |a Cell Membrane: metabolism
|2 MeSH
650 _ 2 |a Cell Membrane: chemistry
|2 MeSH
650 _ 2 |a Protein Binding
|2 MeSH
650 _ 2 |a Endoplasmic Reticulum: metabolism
|2 MeSH
650 _ 2 |a Amino Acid Motifs
|2 MeSH
650 _ 2 |a Hydrophobic and Hydrophilic Interactions
|2 MeSH
700 1 _ |a Verwei, Nino
|0 0000-0003-2464-6896
|b 1
700 1 _ |a Hoffmann, Christian
|0 P:(DE-2719)9000582
|b 2
700 1 _ |a Chodnicki, Paweł
|0 0000-0003-4563-2469
|b 3
700 1 _ |a Sansevrino, Roberto
|0 P:(DE-2719)9000736
|b 4
700 1 _ |a Pyne, Partha
|b 5
700 1 _ |a Wang, Han
|0 P:(DE-2719)9001572
|b 6
700 1 _ |a van Hilten, Niek
|0 0000-0003-1204-2489
|b 7
700 1 _ |a Aschmann, Dennis
|b 8
700 1 _ |a Kros, Alexander
|0 0000-0002-3983-3048
|b 9
700 1 _ |a Andreas, Loren
|b 10
700 1 _ |a Czub, Jacek
|0 0000-0003-3639-6935
|b 11
700 1 _ |a Milovanovic, Dragomir
|0 P:(DE-2719)9000670
|b 12
700 1 _ |a Risselada, Herre Jelger
|0 0000-0003-1410-6570
|b 13
773 _ _ |a 10.1038/s41467-025-63769-5
|g Vol. 16, no. 1, p. 9275
|0 PERI:(DE-600)2553671-0
|n 1
|p 9275
|t Nature Communications
|v 16
|y 2025
|x 2041-1723
856 4 _ |u https://pub.dzne.de/record/281795/files/DZNE-2025-01185.pdf
|y Restricted
856 4 _ |u https://pub.dzne.de/record/281795/files/DZNE-2025-01185.pdf?subformat=pdfa
|x pdfa
|y Restricted
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 2
|6 P:(DE-2719)9000582
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 4
|6 P:(DE-2719)9000736
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 6
|6 P:(DE-2719)9001572
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 12
|6 P:(DE-2719)9000670
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-351
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Brain Function
|x 0
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b NAT COMMUN : 2022
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2024-01-30T07:48:07Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2024-01-30T07:48:07Z
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Peer review
|d 2024-01-30T07:48:07Z
915 _ _ |a Creative Commons Attribution CC BY (No Version)
|0 LIC:(DE-HGF)CCBYNV
|2 V:(DE-HGF)
|b DOAJ
|d 2024-01-30T07:48:07Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1040
|2 StatID
|b Zoological Record
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1060
|2 StatID
|b Current Contents - Agriculture, Biology and Environmental Sciences
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1150
|2 StatID
|b Current Contents - Physical, Chemical and Earth Sciences
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2025-01-02
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2025-01-02
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2025-01-02
915 _ _ |a IF >= 15
|0 StatID:(DE-HGF)9915
|2 StatID
|b NAT COMMUN : 2022
|d 2025-01-02
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2025-01-02
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2025-01-02
920 1 _ |0 I:(DE-2719)1813002
|k AG Milovanovic (Berlin)
|l Molecular Neuroscience
|x 0
980 _ _ |a journal
980 _ _ |a EDITORS
980 _ _ |a VDBINPRINT
980 _ _ |a I:(DE-2719)1813002
980 _ _ |a UNRESTRICTED

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21