Structural basis for LMBD1-dependent trafficking and cobalamin export of ABCD4 - PubMed
3 hours ago
- #LMBD1
- #ABCD4
- #cobalamin transport
- ABCD4, a cobalamin exporter, relies on chaperone LMBD1 for trafficking to lysosomes, unlike most lysosomal membrane proteins.
- Cryo-EM structures of ABCD4-LMBD1 complex reveal lumen-open, substrate-bound, and cytosol-open states, with LMBD1's nine transmembrane helices and cytosolic domain interacting with ABCD4.
- Disruption of ABCD4-LMBD1 interactions impairs lysosomal trafficking, linking to inherited cobalamin metabolism disorders.
- Structural and biochemical analyses elucidate cobalamin recognition and conformational changes during transport cycle.
- Study provides molecular insights into cobalamin metabolism and a chaperone-assisted trafficking mechanism for lysosomal transporters.