The regulatory domains of the lipid exporter ABCA1 form domain swapped latches.

ABSTRACT: ABCA1 and ABCA4 are enigmatic because they transport substrates in opposite directions yet share >50% amino acid identity. ABCA4 imports lipid conjugates but ABCA1 exports lipids. Both hydrolyze ATP to drive transport, and both contain cytoplasmic regulatory domains (RDs) following nucleotide-binding domains (NBDs) in the primary structure. The tertiary structures of several ABC importers, including ABCA4, show that each RD forms a domain-swapped latch that locks onto the opposing RD and holds the NBDs close together. Crucially, sequences encoding the RDs and their bridges are among the most conserved in the entire ABC-A subfamily. In the original cryo-EM structure of ABCA1, the RDs were modeled without crossover. After close inspection of that cryo-EM density map and the recent structure

SUBMITTER: Aller SG 

PROVIDER: S-EPMC8815970 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature