Structure of Vps26B and Mapping of its Interaction with the Retromer Protein Complex

Collins, Brett M., Norwood, Suzanne J., Kerr, Markus C., Mahony, Donna, Seaman, Matthew N. J. and Teasdale, Rohan D. (2008) Structure of Vps26B and Mapping of its Interaction with the Retromer Protein Complex. Traffic, 9 3: 366-379. doi:10.1111/j.1600-0854.2007.00688.x

Author Collins, Brett M.
Norwood, Suzanne J.
Kerr, Markus C.
Mahony, Donna
Seaman, Matthew N. J.
Teasdale, Rohan D.
Title Structure of Vps26B and Mapping of its Interaction with the Retromer Protein Complex
Journal name Traffic   Check publisher's open access policy
ISSN 1398-9219
Publication date 2008-03
Year available 2007
Sub-type Article (original research)
DOI 10.1111/j.1600-0854.2007.00688.x
Volume 9
Issue 3
Start page 366
End page 379
Total pages 13
Place of publication Copenhagen
Publisher Blackwell Munksgaard
Collection year 2008
Language eng
Subject C1
270103 Protein Targeting and Signal Transduction
780105 Biological sciences
Abstract Retromer is a heteromeric protein complex with important roles in endosomal membrane trafficking, most notably in the retrograde transport of lysosomal hydrolase receptors from endosomes to the Golgi. The core of retromer is composed of three subunits vacuolar protein sorting (Vps)35, Vps26 and Vps29, and in mammals, there are two paralogues of the medium subunit Vps26A and Vps26B. We find that both Vps26A and Vps26B bind to Vps35/Vps29 with nanomolar affinity and compete for a single-binding site to define distinct retromer complexes in vitro and in vivo. We have determined the crystal structure of mouse Vps26B and compare this structure with that of Vps26A. Vps26 proteins have a striking similarity to the arrestin family of proteins that regulate the signalling and endocytosis of G-protein-coupled receptors, although we observe that surface residues involved in arrestin function are not conserved in Vps26. Using structure-based mutagenesis, we show that both Vps26A and Vps26B are incorporated into retromer complexes through binding of Vps35 to a highly conserved surface patch within the C-terminal subdomain and that this interaction is required for endosomal recruitment of the proteins.
Keyword arrestin
fibronectin domain
isothermal titration calorimetry
sorting nexin
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes Published Online: 11 Dec 2007

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
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Created: Fri, 11 Apr 2008, 14:31:25 EST by Cody Mudgway on behalf of Institute for Molecular Bioscience