Engineering of a mammalian VMAT2 for cryo-EM analysis results in non-canonical protein folding.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39095428.
- Also identified by DOI 10.1038/s41467-024-50934-5 and PMC identifier 11297040.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Cryoelectron Microscopy
- Protein Folding
- Vesicular Monoamine Transport Proteins
- Protein Engineering