A large-scale conformational change couples membrane recruitment to cargo binding in the AP2 clathrin adaptor complex

Jackson, Lauren P., Kelly, Bernard T., McCoy, Airlie J., Gaffry, Thomas, James, Leo C., Collins, Brett M., Honing, Stefan, Evans, Philip R. and Owen, David J. (2010) A large-scale conformational change couples membrane recruitment to cargo binding in the AP2 clathrin adaptor complex. Cell, 141 7: 1220-1229. doi:10.1016/j.cell.2010.05.006

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ207398.pdf HERDC combined – not publicly available application/pdf 157.13KB 0

Author Jackson, Lauren P.
Kelly, Bernard T.
McCoy, Airlie J.
Gaffry, Thomas
James, Leo C.
Collins, Brett M.
Honing, Stefan
Evans, Philip R.
Owen, David J.
Title A large-scale conformational change couples membrane recruitment to cargo binding in the AP2 clathrin adaptor complex
Journal name Cell   Check publisher's open access policy
ISSN 0092-8674
1097-4172
Publication date 2010-06-25
Sub-type Article (original research)
DOI 10.1016/j.cell.2010.05.006
Volume 141
Issue 7
Start page 1220
End page 1229
Total pages 10
Editor Emilie Marcus
Meredith Adinolfi
Place of publication Cambridge, M.A., U.S.
Publisher Cell Press
Collection year 2011
Language eng
Subject 0601 Biochemistry and Cell Biology
C1
Formatted abstract
The AP2 adaptor complex (α, β2, σ2, and μ2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P2-containing membranes and transmembrane protein cargo. In the " locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxΦ on the C-terminal domain of μ2 (C-μ2) and [ED]xxxL[LI] on σ2, are blocked by parts of β2. Using protein crystallography, we show that AP2 undergoes a large conformational change in which C-μ2 relocates to an orthogonal face of the complex, simultaneously unblocking both cargo-binding sites; the previously unstructured μ2 linker becomes helical and binds back onto the complex. This structural rearrangement results in AP2's four PtdIns4,5P2- and two endocytic motif-binding sites becoming coplanar, facilitating their simultaneous interaction with PtdIns4,5P2/cargo-containing membranes. Using a range of biophysical techniques, we show that the endocytic cargo binding of AP2 is driven by its interaction with PtdIns4,5P2-containing membranes.
© 2010 Elsevier Inc.
Keyword Coated vesicles
Structural explanation
Sorting signals
Mediated endocytosis
Molecular-graphics
Phase information
Appendage domain
Alpha-adaptin
Proteins
Recognition
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 136 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 141 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sun, 11 Jul 2010, 10:08:00 EST