4H8S
Crystal structure of human APPL2BARPH domain
Summary for 4H8S
| Entry DOI | 10.2210/pdb4h8s/pdb |
| Related | 2ELB 2Q12 2Q13 2Z0N 2Z0O |
| Descriptor | DCC-interacting protein 13-beta (1 entity in total) |
| Functional Keywords | bar domain, pleckstrin homology domain, adaptor protein, rab binding, signaling protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Early endosome membrane; Peripheral membrane protein: Q8NEU8 |
| Total number of polymer chains | 4 |
| Total formula weight | 184484.88 |
| Authors | Martin, J.L.,King, G.J. (deposition date: 2012-09-23, release date: 2012-10-17, Last modification date: 2023-09-20) |
| Primary citation | King, G.J.,Stockli, J.,Hu, S.H.,Winnen, B.,Duprez, W.G.,Meoli, C.C.,Junutula, J.R.,Jarrott, R.J.,James, D.E.,Whitten, A.E.,Martin, J.L. Membrane Curvature Protein Exhibits Interdomain Flexibility and Binds a Small GTPase. J.Biol.Chem., 287:40996-41006, 2012 Cited by PubMed 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 co-evolved over time. Isothermal titration calorimetry data reveal the interaction between APPL2 and Rab31 has a K(d) of 140 nM. Together with other biophysical data, we conclude the stoichiometry of the complex is 2:2. PubMed: 23055524DOI: 10.1074/jbc.M112.349803 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.5 Å) |
Structure validation
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