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

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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

Title: Cholesterol-recognition motifs in the transmembrane domain of the tyrosine kinase receptor family : The case of TRKB
Author: Cannarozzo, Cecilia; Fred, Senem Merve; Girych, Mykhailo; Biojone, Caroline; Enkavi, Giray; Rog, Tomasz; Vattulainen, Ilpo Tapio; Casarotto, Plinio C.; Castren, Eero
Contributor organization: Neuroscience Center
Materials Physics
Department of Physics
Date: 2021-05
Language: eng
Number of pages: 12
Belongs to series: European Journal of Neuroscience
ISSN: 0953-816X
DOI: https://doi.org/10.1111/ejn.15218
URI: http://hdl.handle.net/10138/330691
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.
Subject: 3112 Neurosciences
BDNF
cholesterol
recognition motif
TRKB
tyrosine kinase family
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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