iBRET Screen of the ABCD1 Peroxisomal Network and Mutation-Induced Network Perturbations.

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 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.

• Authors: Amelie S Lotz-Havla, Mathias Woidy, Philipp Guder, Caroline C Friedel, Julian M Klingbeil, Ana-Maria Bulau, Anja Schultze, Ilona Dahmen, Heidi Noll-Puchta, Stephan Kemp, Ralf Erdmann, Ralf Zimmer, Ania C Muntau, Søren W Gersting
• Journal: Journal of proteome research (J Proteome Res) Vol. 20 Issue 9 Pg. 4366-4380 (09 03 2021) ISSN: 1535-3907 [Electronic] United States
• PMID: 34383492 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• ATP Binding Cassette Transporter, Subfamily D, Member 1
• ATP-Binding Cassette Transporters
• Fatty Acids

Topics

• ATP Binding Cassette Transporter, Subfamily D, Member 1 (genetics)
• ATP-Binding Cassette Transporters (genetics, metabolism)
• Animals
• Energy Transfer
• Fatty Acids
• Informatics
• Mutation