@Article{LotzHavla2021, author = {Lotz-Havla, Amelie S. and Woidy, Mathias and Guder, Philipp and Friedel, Caroline C. and Klingbeil, Julian M. and Bulau, Ana-Maria and Schultze, Anja and Dahmen, Ilona and Noll-Puchta, Heidi and Kemp, Stephan and Erdmann, Ralf and Zimmer, Ralf and Muntau, Ania C. and Gersting, Sören W.}, journal = {Journal of proteome research}, title = {iBRET Screen of the ABCD1 Peroxisomal Network and Mutation-Induced Network Perturbations.}, year = {2021}, issn = {1535-3907}, month = sep, pages = {4366--4380}, volume = {20}, abstract = {Mapping the network of proteins provides a powerful means to investigate the function of disease genes and to unravel the molecular basis of phenotypes. We present an automated informatics-aided and bioluminescence resonance energy transfer-based approach (iBRET) enabling high-confidence detection of protein-protein interactions in living mammalian cells. A screen of the ABCD1 protein, which is affected in X-linked adrenoleukodystrophy (X-ALD), against an organelle library of peroxisomal proteins demonstrated applicability of iBRET for large-scale experiments. We identified novel protein-protein interactions for ABCD1 (with ALDH3A2, DAO, ECI2, FAR1, PEX10, PEX13, PEX5, PXMP2, and PIPOX), mapped its position within the peroxisomal protein-protein interaction network, and determined that pathogenic missense variants in alter the interaction with selected binding partners. These findings provide mechanistic insights into pathophysiology of X-ALD and may foster the identification of new disease modifiers.}, chemicals = {ATP Binding Cassette Transporter, Subfamily D, Member 1, ATP-Binding Cassette Transporters, Fatty Acids}, citation-subset = {IM}, completed = {2021-10-28}, country = {United States}, doi = {10.1021/acs.jproteome.1c00330}, issn-linking = {1535-3893}, issue = {9}, keywords = {ATP Binding Cassette Transporter, Subfamily D, Member 1, genetics; ATP-Binding Cassette Transporters, genetics, metabolism; Animals; Energy Transfer; Fatty Acids; Informatics; Mutation; ABCD1; BRET; FAR1; X-ALD; bioluminescence resonance energy transfer; fatty acids; interactome; lipid droplets; living cells; protein?protein interaction; screening}, nlm-id = {101128775}, owner = {NLM}, pmid = {34383492}, pubmodel = {Print-Electronic}, pubstate = {ppublish}, revised = {2021-10-28}, }