A structure-based mechanism for initiation of AP-3 coated vesicle formation.

ABSTRACT: Adaptor protein complex 3 (AP-3) mediates cargo sorting from endosomes to lysosomes and lysosome-related organelles. Recently, it was shown that AP-3 is in a constitutively open, active conformation compared to the related AP-1 and AP-2 coat complexes, which are inactive until undergoing large conformational changes upon membrane recruitment. How AP-3 is regulated is therefore an open question. To understand the mechanism of AP-3 membrane recruitment and activation, we reconstituted the core of human AP-3 and determined multiple structures in the soluble and membrane-bound states using electron cryo-microscopy (cryo-EM). Similar to yeast AP-3, human AP-3 is in a constitutively open conformation, with the cargo-binding domain of the μ3 subunit conformationally free. To reconstitute AP-3 act

SUBMITTER: Begley M 

PROVIDER: S-EPMC11185636 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature