iBRET Screen of the ABCD1 Peroxisomal Network and Mutation-Induced Network Perturbations
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iBRET Screen of the ABCD1 Peroxisomal Network and Mutation-Induced Network Perturbations. / Lotz-Havla, Amelie S; Woidy, Mathias; Guder, Philipp; Friedel, Caroline C; Klingbeil, Julian M; Bulau, Ana-Maria; Schultze, Anja; Dahmen, Ilona; Noll-Puchta, Heidi; Kemp, Stephan; Erdmann, Ralf; Zimmer, Ralf; Muntau, Ania C; Gersting, Søren W.
in: J PROTEOME RES, Jahrgang 20, Nr. 9, 03.09.2021, S. 4366-4380.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - iBRET Screen of the ABCD1 Peroxisomal Network and Mutation-Induced Network Perturbations
AU - Lotz-Havla, Amelie S
AU - Woidy, Mathias
AU - Guder, Philipp
AU - Friedel, Caroline C
AU - Klingbeil, Julian M
AU - Bulau, Ana-Maria
AU - Schultze, Anja
AU - Dahmen, Ilona
AU - Noll-Puchta, Heidi
AU - Kemp, Stephan
AU - Erdmann, Ralf
AU - Zimmer, Ralf
AU - Muntau, Ania C
AU - Gersting, Søren W
PY - 2021/9/3
Y1 - 2021/9/3
N2 - 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 ABCD1 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.
AB - 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 ABCD1 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.
KW - ATP Binding Cassette Transporter, Subfamily D, Member 1/genetics
KW - ATP-Binding Cassette Transporters/genetics
KW - Animals
KW - Energy Transfer
KW - Fatty Acids
KW - Informatics
KW - Mutation
U2 - 10.1021/acs.jproteome.1c00330
DO - 10.1021/acs.jproteome.1c00330
M3 - SCORING: Journal article
C2 - 34383492
VL - 20
SP - 4366
EP - 4380
JO - J PROTEOME RES
JF - J PROTEOME RES
SN - 1535-3893
IS - 9
ER -