Assembly and Solution Structure of the Core Retromer Protein Complex

Retromer is a peripheral membrane protein complex that has pleiotropic roles in endosomal membrane trafficking. The core of retromer possesses three subunits, VPS35, VPS29 and VPS26, that play different roles in binding to cargo, regulatory proteins and complex stabilization. We have performed an in...

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Bibliographic Details
Published in:Traffic (Copenhagen, Denmark) Denmark), 2011-01, Vol.12 (1), p.56-71
Main Authors: Norwood, Suzanne J., Shaw, Daniel J., Cowieson, Nathan P., Owen, David J., Teasdale, Rohan D., Collins, Brett M.
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Amino Acid Sequence
Calorimetry
Conserved Sequence
Crystallography, X-Ray
Humans
ITC
Models, Molecular
Molecular Sequence Data
Multiprotein Complexes - chemistry
Quantum Theory
retromer
SAXS
SNX
Solutions - chemistry
sorting nexin
Vesicular Transport Proteins - chemistry
VPS26
VPS29
VPS35
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Summary:Retromer is a peripheral membrane protein complex that has pleiotropic roles in endosomal membrane trafficking. The core of retromer possesses three subunits, VPS35, VPS29 and VPS26, that play different roles in binding to cargo, regulatory proteins and complex stabilization. We have performed an investigation of the thermodynamics of core retromer assembly using isothermal titration calorimetry (ITC) demonstrating that VPS35 acts as the central subunit to which VPS29 and VPS26 bind independently. Furthermore, we confirm that the conserved PRLYL motif of the large VPS35 subunit is critical for direct VPS26 interaction. Heat capacity measurements of VPS29 and VPS26 binding to VPS35 indicate extensive binding interfaces and suggest conformational alterations in VPS29 or VPS35 upon complex formation. Solution studies of the retromer core using small‐angle X‐ray scattering allow us to propose a model whereby VPS35 forms an extended platform with VPS29 and VPS26 bound at distal ends, with the potential for forming dimeric assemblies.
ISSN:1398-9219
1600-0854
DOI:10.1111/j.1600-0854.2010.01124.x