title: Cholesterol Interaction with the MAGUK Protein Family Member, MPP1, via CRAC and CRAC-Like Motifs: An In Silico Docking Analysis.
abstract: Cholesterol is essential for the proper organization of the biological membrane. Therefore, predicting which proteins can bind cholesterol is important in understanding how proteins participate in lateral membrane organization. In this study, a simple bioinformatics approach was used to establish whether MPP1, a member of the MAGUK protein family, is capable of binding cholesterol. Modelled and experimentally-validated fragment structures were mined from online resources and searched for CRAC and CRAC-like motifs. Several of these motifs were found in the primary structure of MPP1, and these were structurally visualized to see whether they localized to the protein surface. Since all of the CRAC and CRAC-like motifs were found at the surface of MPP1 domains, in silico docking experiments were performed to assess the possibility of interaction between CRAC motifs and cholesterol. The results obtained show that MPP1 can bind cholesterol via CRAC and CRAC-like motifs with moderate to high affinity (KI 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. Data presented here may help to understand at least one of the molecular mechanisms via which MPP1 affects lateral organization of the membrane.
authors.affiliation: Department of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, Wrocław, Poland.
authors.forename: Marcin A
authors.initials: MA
authors.lastname: Listowski
authors.affiliation: Department of Molecular Biology, University of Zielona Góra, Zielona Góra, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Leluk
authors.affiliation: Department of Biomedical Engineering, Wrocław University of Technology, Wrocław, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kraszewski
authors.affiliation: Department of Cytobiochemistry, Faculty of Biotechnology, University of Wrocław, Wrocław, Poland; Department of Molecular Biology, University of Zielona Góra, Zielona Góra, Poland.
authors.forename: Aleksander F
authors.initials: AF
authors.lastname: Sikorski
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001798:Blood Proteins / Q000737:chemistry* / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs
chemical_list: D001798:Blood Proteins; C089465:MPP1 protein, human; D008565:Membrane Proteins; D002784:Cholesterol