Structure and plasticity of Endophilin and Sorting Nexin 9.

Publication Type:

Journal Article


Structure, Volume 16, Issue 10, p.1574-87 (2008)


Adaptor Proteins, Signal Transducing, Animals, Crystallography, X-Ray, Humans, Kinetics, Mice, Models, Biological, Models, Molecular, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Quaternary, Protein Structure, Secondary, Protein Structure, Tertiary, Scattering, Small Angle, Sorting Nexins, Vesicular Transport Proteins, X-Ray Diffraction


<p>Endophilin and Sorting Nexin 9 (Snx9) play key roles in endocytosis by membrane curvature sensing and remodeling via their Bin/Amphiphysin/Rvs (BAR) domains. BAR and the related F-BAR domains form dimeric, crescent-shaped units that occur N- or C-terminally to other lipid-binding, adaptor, or catalytic modules. In crystal structures, the PX-BAR unit of Snx9 (Snx9(PX-BAR)) adopts an overall compact, moderately curved conformation. SAXS-based solution studies revealed an alternative, more curved state of Snx9(PX-BAR) in which the PX domains are flexibly connected to the BAR domains, providing a model for how Snx9 exhibits lipid-dependent curvature preferences. In contrast, Endophilin appears to be rigid in solution, and the SH3 domains are located at the distal tips of a BAR domain dimer with fixed curvature. We also observed tip-to-tip interactions between the BAR domains in a trigonal crystal form of Snx9(PX-BAR) reminiscent of functionally important interactions described for F-BAR domains.</p>