Cholesterol Interaction with the MAGUK Protein Family Member, MPP1, via CRAC and CRAC-Like Motifs: An In Silico Docking Analysis

Listowski, Marcin A.; Leluk, Jacek; Kraszewski, Sebastian; Sikorski, Aleksander F.

doi:10.1371/journal.pone.0133141

Cited by 21 publications

(20 citation statements)

References 49 publications

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“…Many cholesterol poses were predicted by the docking, with a wide range of interaction energies. However, it is well known that in the presence of strong hydrophobic interactions, as in the case of cholesterol, docking procedures are not always straightforward [45]. Therefore, only those poses which fulfill both higher scores (lower binding energy) and the vicinity to some CARC-CRAC motifs were shown in the figures (Figures 9b and c).…”

Section: In Silico Analysis Of the Interaction Of Octn1 With Cholesterolmentioning

confidence: 99%

Effect of Cholesterol on the Organic Cation Transporter OCTN1 (SLC22A4)

Pochini

Pappacoda

Galluccio

et al. 2020

IJMS

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The effect of cholesterol was investigated on the OCTN1 transport activity measured as [ 14 C]-tetraethylamonium or [ 3 H]-acetylcholine uptake in proteoliposomes reconstituted with native transporter extracted from HeLa cells or the human recombinant OCTN1 over-expressed in E. coli. Removal of cholesterol from the native transporter by MβCD before reconstitution led to impairment of transport activity. A similar activity impairment was observed after treatment of proteoliposomes harboring the recombinant (cholesterol-free) protein by MβCD, suggesting that the lipid mixture used for reconstitution contained some cholesterol. An enzymatic assay revealed the presence of 10 µg cholesterol/mg total lipids corresponding to 1% cholesterol in the phospholipid mixture used for the proteoliposome preparation. On the other way around, the activity of the recombinant OCTN1 was stimulated by adding the cholesterol analogue, CHS to the proteoliposome preparation. Optimal transport activity was detected in the presence of 83 µg CHS/ mg total lipids for both [ 14 C]-tetraethylamonium or [ 3 H]-acetylcholine uptake. Kinetic analysis of transport demonstrated that the stimulation of transport activity by CHS consisted in an increase of the Vmax of transport with no changes of the Km. Altogether, the data suggests a direct interaction of cholesterol with the protein. A further support to this interpretation was given by a docking analysis indicating the interaction of cholesterol with some protein sites corresponding to CARC-CRAC motifs. The observed direct interaction of cholesterol with OCTN1 points to a possible direct influence of cholesterol on tumor cells or on acetylcholine transport in neuronal and non-neuronal cells via OCTN1.

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Section: In Silico Analysis Of the Interaction Of Octn1 With Cholesterolmentioning

confidence: 99%

Effect of Cholesterol on the Organic Cation Transporter OCTN1 (SLC22A4)

Pochini

Pappacoda

Galluccio

et al. 2020

IJMS

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“…The addition of MPP1 to the subphase underneath a monolayer of a lipid mixture without cholesterol induced a smaller change in the area at constant surface pressure, compared with that obtained for the same lipid mixture containing cholesterol. This decrease in area may indicate a structural modification, or molecular rearrangement, within the lipid monolayer that is specific to the type of monolayer composition, that is, either the MPP1 can bind directly to cholesterol, as shown by Listowski et al (2015) or that cholesterol modulates the arrangement of the lipid monolayer, i.e. inducing a phase separation (e.g.…”

Section: B a D C Ementioning

confidence: 99%

“…Our previous simple in silico modelling study on MPP1 (Listowski et al 2015) showed that this protein contains two hydrophobic/amphipathic stretches of ~12-18 amino acid residues which could be responsible for the binding or penetration of MPP1 to lipid bi-and mono-layers via hydrophobic interactions. The effect of ionic strength and pH would shed some light on this issue.…”

Section: B a D C Ementioning

confidence: 99%

MPP1 interacts with DOPC/SM/cholesterol in an artificial membrane system using Langmuir-Blodgett monolayer

Elderdfi

Zegarlińska²,

Jones³

et al. 2017

gpb

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The interaction between membrane palmitoylated protein -1 (MPP1) with lipid bi- and mono-layers composed of a DOPC/SM/Chol mixture was investigated. MPP1 co-migrates with liposomes to the top of the liposome flotation gradient, indicating binding of MPP1 with liposomes. The injection of MPP1 into the subphase of an LB monolayer of the above lipid composition induced an increase in surface pressure, indicating that MPP1 molecules were incorporated into the lipid monolayer. The compressibility modulus isotherms of MPP1, lipids and lipid-MPP1 films have essentially different shapes from one another. Pure MPP1 isotherms were characterized by a peak in surface pressure of 25-35 mNm-1. This transition disappears in isotherms obtained with lipid monolayers in the presence of MPP1, which suggests an interaction between the protein and the lipid monolayers. In addition, this interaction is sensitive to the presence of cholesterol in the lipid monolayer, as adding of MPP1 into the subphase of lipid monolayers containing cholesterol resulted in a much larger increase in surface area than when MPP1 is injected into the subphase of a lipid monolayer devoid of cholesterol. In conclusion, the data demonstrates that MPP1 interacts with lipid mixtures in two different model membrane systems.

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“…We believe that flotillin-1 and -2 are important components of these nanoclusters, which was confirmed by the fact that flotillins are found in the DRM residual fraction even after treatment with beta methyl cyclodextrin. Binding of palmitoylated MPP1 to the pre-existing nanocomplexes via flotillins and perhaps via cholesterol-binding regions as was recently documented [75,[84][85][86] induces their fusion and stabilizes them as membrane resting-state rafts, which are larger (~20 nm) in diameter [90], more stable (~1 s), detergent-resistant, and which become functional (see Fig. 3).…”

Section: Mpp1 Is the Resting State Raft Organizing Protein In Erythromentioning

confidence: 80%

“…The obtained results show that MPP1 can bind cholesterol via CRAC and CRAC-like motifs with moderate to high affinity (K I in the nano-to micro-molar range). It was also found that palmitoylation-mimicking mutations (C/F or C/M) did not affect the affinity of MPP1 towards cholesterol [84]. Further studies on recombinant MPP1 interactions in simple Langmuir monolayer technique revealed that injection of MPP1 into the subphase of an LB monolayer composed of DOPC/SM/Chol (1:1:1 molar ratio) induced an increase in surface pressure, indicating that MPP1 molecules were incorporated into the lipid monolayer.…”

Section: Mpp1 Interacts With Cholesterol and Lipidsmentioning

confidence: 97%

MPP1-based mechanism of resting state raft organization in the plasma membrane. Is it a general or specialized mechanism in erythroid cells?

Trybus

Niemiec

Biernatowska

et al. 2019

Folia Histochem Cytobiol.

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Biological membranes are organized in various microdomains, one of the best known being called membrane rafts. The major function of these is thought to organize signaling partners into functional complexes. An important protein found in membrane raft microdomains of erythroid and other blood cells is MPP1 (membrane palmitoylated protein 1)/p55. MPP1 (p55) belongs to the MAGUK (membrane-associated guanylate kinase homolog) family and it is a major target of palmitoylation in the red blood cells (RBCs) membrane. The wellknown function of this protein is to participate in formation of the junctional complex of the erythrocyte membrane skeleton. However, its function as a "raft organizer" is not well understood. In this review we focus on recent reports concerning MPP1 participation in membrane rafts organization in erythroid cells, including its role in signal transduction. Currently it is not known whether MPP1 could have a similar role in cell types other than erythroid lineage. We present also preliminary data regarding the expression level of MPP1 gene in several non-erythroid cell lines.

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Cholesterol Interaction with the MAGUK Protein Family Member, MPP1, via CRAC and CRAC-Like Motifs: An In Silico Docking Analysis

Cited by 21 publications

References 49 publications

Effect of Cholesterol on the Organic Cation Transporter OCTN1 (SLC22A4)

Effect of Cholesterol on the Organic Cation Transporter OCTN1 (SLC22A4)

MPP1 interacts with DOPC/SM/cholesterol in an artificial membrane system using Langmuir-Blodgett monolayer

MPP1-based mechanism of resting state raft organization in the plasma membrane. Is it a general or specialized mechanism in erythroid cells?

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