Solving the structure of retromer

The retromer complex
The retromer complex (red, yellow and green).

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Retromer’s 3D structure improves understanding of cellular sorting and packaging

Retromer is a molecular machine that sorts and packs cargo at the cell’s logistics hub, the endosome. It ensures the safe and efficient transport of cellular cargo in all eukaryotes, from baker’s yeast to humans.

An international research team now publishes the full 3D structure of retromer. They used cryo-electron tomography to reveal the structure of the retromer complex assembled on a membrane, allowing a greater understanding of how this molecular machine works.

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The retromer complex (red, yellow and green) forms arch-like structures that reinforce tubular transport vesicles and provide a scaffold interacting with other modules of the sorting machinery, such as sorting nexin proteins (blue).

 

 

 

 

 

 

To achieve this, researchers in John Briggs’ group – formerly at EMBL and now at the Laboratory of Molecular Biology (LMB) – collaborated with scientists at the University of Queensland, the University of Cambridge, and the Max Planck Institute of Biochemistry. They publish their findings in Nature on 17 September 2018.

The full structure of retromer, with its arches, scaffolds and curving membranes, shows how this protein machinery is assembled and gives important insights into its function. It also suggests how mutations in human patients could lead to retromer malfunction, known to lead to neurodegenerative diseases.

For more information, see the LMB story or the press release by the University of Queensland.