Engineering of a mammalian VMAT2 for cryo-EM analysis results in non-canonical protein folding.
Nat Commun
; 15(1): 6511, 2024 Aug 02.
Article
em En
| MEDLINE
| ID: mdl-39095428
ABSTRACT
Vesicular monoamine transporter 2 (VMAT2) belongs to the major facilitator superfamily (MFS), and mediates cytoplasmic monoamine packaging into presynaptic vesicles. Here, we present two cryo-EM structures of VMAT2, with a frog VMAT2 adopting a canonical MFS fold and an engineered sheep VMAT2 adopting a non-canonical fold. Both VMAT2 proteins mediate uptake of a selective fluorescent VMAT2 substrate into cells. Molecular docking, substrate binding and transport analysis reveal potential substrate binding mechanism in VMAT2. Meanwhile, caution is advised when interpreting engineered membrane protein structures.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Engenharia de Proteínas
/
Dobramento de Proteína
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Microscopia Crioeletrônica
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Proteínas Vesiculares de Transporte de Monoamina
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article