Cholesterol-recognition motifs in the transmembrane domain of the tyrosine kinase receptor family : The case of TRKB

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dc.contributor.author Cannarozzo, Cecilia
dc.contributor.author Fred, Senem Merve
dc.contributor.author Girych, Mykhailo
dc.contributor.author Biojone, Caroline
dc.contributor.author Enkavi, Giray
dc.contributor.author Rog, Tomasz
dc.contributor.author Vattulainen, Ilpo Tapio
dc.contributor.author Casarotto, Plinio C.
dc.contributor.author Castren, Eero
dc.date.accessioned 2021-06-07T13:09:01Z
dc.date.available 2021-06-07T13:09:01Z
dc.date.issued 2021-05
dc.identifier.citation Cannarozzo , C , Fred , S M , Girych , M , Biojone , C , Enkavi , G , Rog , T , Vattulainen , I T , Casarotto , P C & Castren , E 2021 , ' Cholesterol-recognition motifs in the transmembrane domain of the tyrosine kinase receptor family : The case of TRKB ' , European Journal of Neuroscience , vol. 53 , no. 10 , pp. 3311-3322 . https://doi.org/10.1111/ejn.15218
dc.identifier.other PURE: 163314908
dc.identifier.other PURE UUID: 136329c9-5ea6-47b4-969a-88927517932b
dc.identifier.other WOS: 000647233700001
dc.identifier.other ORCID: /0000-0002-1402-2791/work/95133946
dc.identifier.other ORCID: /0000-0002-1090-4631/work/95136239
dc.identifier.other ORCID: /0000-0001-7408-3214/work/95136723
dc.identifier.other ORCID: /0000-0003-1992-5014/work/95137064
dc.identifier.uri http://hdl.handle.net/10138/330691
dc.description.abstract Cholesterol is an essential constituent of cell membranes. The discovery of cholesterol-recognition amino acid consensus (CRAC) motif in proteins indicated a putative direct, non-covalent interaction between cholesterol and proteins. In the present study, we evaluated the presence of a CRAC motif and its inverted version (CARC) in the transmembrane region (TMR) of the tyrosine kinase receptor family (RTK) in several species using in silico methods. CRAC motifs were found across all species analyzed, while CARC was found only in vertebrates. The tropomyosin-related kinase B (TRKB), a member of the RTK family, through interaction with its endogenous ligand brain-derived neurotrophic factor (BDNF) is a core participant in the neuronal plasticity process and exhibits a CARC motif in its TMR. Upon identifying the conserved CARC motif in the TRKB, we performed molecular dynamics simulations of the mouse TRKB.TMR. The simulations indicated that cholesterol interaction with the TRKB CARC motif occurs mainly at the central Y433 residue. Our binding assay suggested a bell-shaped effect of cholesterol on BDNF interaction with TRKB receptors, and our results suggest that CARC/CRAC motifs may play a role in the function of the RTK family TMR. en
dc.format.extent 12
dc.language.iso eng
dc.relation.ispartof European Journal of Neuroscience
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 3112 Neurosciences
dc.subject BDNF
dc.subject cholesterol
dc.subject recognition motif
dc.subject TRKB
dc.subject tyrosine kinase family
dc.title Cholesterol-recognition motifs in the transmembrane domain of the tyrosine kinase receptor family : The case of TRKB en
dc.type Article
dc.contributor.organization Neuroscience Center
dc.contributor.organization Materials Physics
dc.contributor.organization Department of Physics
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1111/ejn.15218
dc.relation.issn 0953-816X
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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