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A molecular code for endosomal recycling of phosphorylated cargos by the SNX27–retromer complex
- Source :
- Nature Structural & Molecular Biology. 23:921-932
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Recycling of internalized receptors from endosomal compartments is essential for the receptors' cell-surface homeostasis. Sorting nexin 27 (SNX27) cooperates with the retromer complex in the recycling of proteins containing type I PSD95-Dlg-ZO1 (PDZ)-binding motifs. Here we define specific acidic amino acid sequences upstream of the PDZ-binding motif required for high-affinity engagement of the human SNX27 PDZ domain. However, a subset of SNX27 ligands, such as the β2 adrenergic receptor and N-methyl-D-aspartate (NMDA) receptor, lack these sequence determinants. Instead, we identified conserved sites of phosphorylation that substitute for acidic residues and dramatically enhance SNX27 interactions. This newly identified mechanism suggests a likely regulatory switch for PDZ interaction and protein transport by the SNX27-retromer complex. Defining this SNX27 binding code allowed us to classify more than 400 potential SNX27 ligands with broad functional implications in signal transduction, neuronal plasticity and metabolite transport.
- Subjects :
- Models, Molecular
0301 basic medicine
SNX27
Endosome
PDZ domain
PDZ Domains
Endosomes
03 medical and health sciences
0302 clinical medicine
Structural Biology
Humans
Amino Acid Sequence
Protein Interaction Maps
Phosphorylation
Sorting Nexins
Molecular Biology
Peptide sequence
Chemistry
Cell biology
Transport protein
Molecular Docking Simulation
Retromer complex
Protein Transport
Sorting nexin
HEK293 Cells
030104 developmental biology
Receptors, Glutamate
Signal transduction
Sequence Alignment
030217 neurology & neurosurgery
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 15459985 and 15459993
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Nature Structural & Molecular Biology
- Accession number :
- edsair.doi.dedup.....48ae144d167d0687821d3f84c642d702