Membrane curvature protein exhibits interdomain flexibility and binds a small GTPase

King, Gordon J., Stoeckli, Jacqueline, Hu, Shu-Hong, Winnen, Brit, Duprez, Wilko G. A., Meoli, Christopher C., Junutula, Jagath R., Jarrott, Russell J., James, David E., Whitten, Andrew E. and Martin, Jennifer L. (2012) Membrane curvature protein exhibits interdomain flexibility and binds a small GTPase. Journal of Biological Chemistry, 287 49: 40996-41006. doi:10.1074/jbc.M112.349803

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Author King, Gordon J.
Stoeckli, Jacqueline
Hu, Shu-Hong
Winnen, Brit
Duprez, Wilko G. A.
Meoli, Christopher C.
Junutula, Jagath R.
Jarrott, Russell J.
James, David E.
Whitten, Andrew E.
Martin, Jennifer L.
Title Membrane curvature protein exhibits interdomain flexibility and binds a small GTPase
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2012-11-30
Sub-type Article (original research)
DOI 10.1074/jbc.M112.349803
Open Access Status File (Publisher version)
Volume 287
Issue 49
Start page 40996
End page 41006
Total pages 11
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Collection year 2013
Language eng
Formatted abstract
The APPL1 and APPL2 proteins (APPL (adaptor protein, phosphotyrosine interaction, pleckstrin homology (PH) domain, and leucine zipper-containing protein)) are localized to their own endosomal subcompartment and interact with a wide range of proteins and small molecules at the cell surface and in the nucleus. They play important roles in signal transduction through their ability to act as Rab effectors. (Rabs are a family of Ras GTPases involved in membrane trafficking.) Both APPL1 and APPL2 comprise an N-terminal membrane-curving BAR (Bin-amphiphysin-Rvs) domain linked to a PH domain and a C-terminal phosphotyrosine-binding domain. The structure and interactions of APPL1 are well characterized, but little is known about APPL2. Here, we report the crystal structure and low resolution solution structure of the BARPH domains of APPL2. We identify a previously undetected hinge site for rotation between the two domains and speculate that this motion may regulate APPL2 functions. We also identified Rab binding partners of APPL2 and show that these differ from those of APPL1, suggesting that APPL-Rab interaction partners have coevolved over time. Isothermal titration calorimetry data reveal the interaction between APPL2 and Rab31 has a Kd of 140 nM. Together with other biophysical data, we conclude the stoichiometry of the complex is 2:2.
Keyword Pleckstrin homology domain
Linked mental retardation
Small angle scattering
Macromolecular crystallography
Bar domains
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
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