Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes
- PMID: 12737822
- DOI: 10.1016/s0969-2126(03)00068-6
Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes
Abstract
Formation of the mammalian six-layered neocortex depends on a signaling pathway that involves Reelin, the very low-density lipoprotein receptor, the apolipoprotein E receptor-2 (ApoER2), and the adaptor protein Disabled-1 (Dab1). The 1.5 A crystal structure of a complex between the Dab1 phosphotyrosine binding (PTB) domain and a 14-residue peptide from the ApoER2 tail explains the unusual preference of Dab1 for unphosphorylated tyrosine within the NPxY motif of the peptide. Crystals of the complex soaked with the phosphoinositide PI-4,5P(2) (PI) show that PI binds to conserved basic residues on the PTB domain opposite the peptide binding groove. This finding explains how the Dab1 PTB domain can simultaneously bind PI and the ApoER2 tail. Recruitment of the Dab1 PTB domain to PI-rich regions of the plasma membrane may facilitate association with the Reelin receptor cytoplasmic tails to transduce a critical positional cue to migrating neurons.
Similar articles
-
Phosphoinositide binding by the disabled-1 PTB domain is necessary for membrane localization and Reelin signal transduction.J Biol Chem. 2005 Mar 11;280(10):9671-7. doi: 10.1074/jbc.M413356200. Epub 2005 Jan 4. J Biol Chem. 2005. PMID: 15632144
-
Signaling through Disabled 1 requires phosphoinositide binding.Biochem Biophys Res Commun. 2005 Jun 17;331(4):1460-8. doi: 10.1016/j.bbrc.2005.04.064. Biochem Biophys Res Commun. 2005. PMID: 15883038
-
Crystal structures of the Dab homology domains of mouse disabled 1 and 2.J Biol Chem. 2003 Sep 19;278(38):36572-81. doi: 10.1074/jbc.M304384200. Epub 2003 Jun 24. J Biol Chem. 2003. PMID: 12826668
-
Modulation of lipoprotein receptor functions by intracellular adaptor proteins.Cell Signal. 2006 Oct;18(10):1560-71. doi: 10.1016/j.cellsig.2006.03.008. Epub 2006 May 24. Cell Signal. 2006. PMID: 16725309 Review.
-
Structural and evolutionary division of phosphotyrosine binding (PTB) domains.J Mol Biol. 2005 Jan 7;345(1):1-20. doi: 10.1016/j.jmb.2004.10.038. J Mol Biol. 2005. PMID: 15567406 Review.
Cited by
-
The Multirole of Liposomes in Therapy and Prevention of Infectious Diseases.Front Immunol. 2018 Feb 5;9:155. doi: 10.3389/fimmu.2018.00155. eCollection 2018. Front Immunol. 2018. PMID: 29459867 Free PMC article. Review.
-
Structure, sulfatide binding properties, and inhibition of platelet aggregation by a disabled-2 protein-derived peptide.J Biol Chem. 2012 Nov 2;287(45):37691-702. doi: 10.1074/jbc.M112.385609. Epub 2012 Sep 13. J Biol Chem. 2012. PMID: 22977233 Free PMC article.
-
TNS1: Emerging Insights into Its Domain Function, Biological Roles, and Tumors.Biology (Basel). 2022 Oct 26;11(11):1571. doi: 10.3390/biology11111571. Biology (Basel). 2022. PMID: 36358270 Free PMC article. Review.
-
Both the phosphoinositide and receptor binding activities of Dab1 are required for Reelin-stimulated Dab1 tyrosine phosphorylation.Brain Res Mol Brain Res. 2005 Oct 3;139(2):300-5. doi: 10.1016/j.molbrainres.2005.06.001. Brain Res Mol Brain Res. 2005. PMID: 16046028 Free PMC article.
-
Reconstitution of the Reelin signaling pathway in fibroblasts demonstrates that Dab1 phosphorylation is independent of receptor localization in lipid rafts.Mol Cell Biol. 2006 Jan;26(1):19-27. doi: 10.1128/MCB.26.1.19-27.2006. Mol Cell Biol. 2006. PMID: 16354676 Free PMC article.
Publication types
MeSH terms
Substances
Associated data
- Actions
- Actions
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous
