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Functional architecture of the retromer cargo-recognition complex
Aitor Hierro1, Adriana L Rojas, Raul Rojas
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland 20892, USA.
Nature
|September 25, 2007
Summary
The retromer complex, crucial for cellular transport, has its structure revealed. This reveals how VPS29 and VPS35 subunits interact, forming a flexible scaffold for other proteins and cargo.
Area of Science:
- Cell Biology
- Structural Biology
- Molecular Mechanisms
Background:
- The retromer complex plays vital roles in intracellular sorting and transport.
- It comprises a cargo recognition module (VPS26-VPS29-VPS35) and a membrane-targeting module (SNX1/SNX2).
Purpose of the Study:
- To elucidate the structural basis of retromer complex assembly and function.
- To understand the interaction between VPS29 and VPS35 subunits.
Main Methods:
- X-ray crystallography was used to determine the structure of the VPS29-VPS35 subcomplex.
- Electron microscopy visualized the intact VPS26-VPS29-VPS35 complex.
- Hybrid structural modeling integrated crystallographic, microscopy, and bioinformatics data.
Main Results:
- The crystal structure reveals VPS29 acting as a scaffold for VPS35, forming a horseshoe-shaped alpha-helical solenoid.
- Electron microscopy shows the intact complex as a flexible, stick-shaped structure approximately 21 nm long.
- A hybrid model demonstrates an extended VPS35 structure with VPS26 at one end and VPS29 at the other, facilitating interactions with SNX proteins and cargo.
Conclusions:
- The retromer complex possesses an extended, flexible architecture enabling interaction with membranes and diverse cargo.
- This structural understanding provides insights into the molecular mechanisms of retromer-mediated transport processes.
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