4h8s

Crystal structure of human APPL2BARPH domain

spinqualitylabelsall models 4h8s, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4h8s is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease DP13B_HUMAN A chromosomal aberration involving APPL2/DIP13B is found in patients with chromosome 22q13.3 deletion syndrome. Translocation t(12;22)(q24.1;q13.3) with SHANK3/PSAP2. Function DP13B_HUMAN Required for the regulation of cell proliferation in response to extracellular signals mediated by an early endosomal compartment. Links Rab5 to nuclear signal transduction. Publication Abstract from PubMed The APPL1 and APPL2 proteins (APPL=adaptor protein, phosphotyrosine interaction, pleckstrin homology (PH) domain and leucine zipper containing protein) are localised to their own endosomal sub-compartment 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 GTP-ases 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 characterised, 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 co-evolved 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. Membrane-curvature protein exhibits interdomain flexibility and binds a small GTPase.,King GJ, Stoeckli J, Hu SH, Winnen B, Duprez WG, Meoli CC, Junutula JR, Jarrott RJ, James DE, Whitten AE, Martin JL J Biol Chem. 2012 Oct 10. PMID:23055524 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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