Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Low pH-induced conformational change and dimerization of sortilin triggers endocytosed ligand release.
Journal, issue, pages	Nat Commun, Vol. 8, Issue 1, Page 1708, Year 2017
Publish date	Nov 22, 2017
Authors	Nadia Leloup / Philip Lössl / Dimphna H Meijer / Martha Brennich / Albert J R Heck / Dominique M E Thies-Weesie / Bert J C Janssen /
PubMed Abstract	Low pH-induced ligand release and receptor recycling are important steps for endocytosis. The transmembrane protein sortilin, a β-propeller containing endocytosis receptor, internalizes a diverse ...Low pH-induced ligand release and receptor recycling are important steps for endocytosis. The transmembrane protein sortilin, a β-propeller containing endocytosis receptor, internalizes a diverse set of ligands with roles in cell differentiation and homeostasis. The molecular mechanisms of pH-mediated ligand release and sortilin recycling are unresolved. Here we present crystal structures that show the sortilin luminal segment (s-sortilin) undergoes a conformational change and dimerizes at low pH. The conformational change, within all three sortilin luminal domains, provides an altered surface and the dimers sterically shield a large interface while bringing the two s-sortilin C-termini into close proximity. Biophysical and cell-based assays show that members of two different ligand families, (pro)neurotrophins and neurotensin, preferentially bind the sortilin monomer. This indicates that sortilin dimerization and conformational change discharges ligands and triggers recycling. More generally, this work may reveal a double mechanism for low pH-induced ligand release by endocytosis receptors.
External links	Nat Commun / PubMed:29167428 / PubMed Central
Methods	SAS (X-ray synchrotron) / X-ray diffraction
Resolution	2.1 - 4 Å
Structure data	SASDCE7: Monomeric Sortilin at pH 7.4 in the presence of neurotensin Method: SAXS/SANS SASDCF7: Dimeric Sortilin at pH 7.4 in the presence of neurotensin Method: SAXS/SANS SASDCW5: Dimeric Sortilin at pH 7.4 (Sortilin, also: Neurotensin-receptor 3, Sort1, also: NTR3) Method: SAXS/SANS SASDCX5: Monomeric Sortilin at pH 5.5 (Sortilin 1 A464E alias Neurotensin-receptor 3 A464E) Method: SAXS/SANS SASDCY5: Dimeric Sortilin at pH 5.5 (Sortilin, also: Neurotensin-receptor 3, Sort1, also: NTR3) Method: SAXS/SANS SASDCZ5: Monomeric Sortilin at pH 7.4 (Sortilin 1 A464E alias Neurotensin-receptor 3 A464E) Method: SAXS/SANS PDB-5nmr: Monomeric mouse Sortilin extracellular domain Method: X-RAY DIFFRACTION / Resolution: 2.1 Å PDB-5nmt: Dimer structure of Sortilin ectodomain crystal form 1, 2.3A Method: X-RAY DIFFRACTION / Resolution: 2.3 Å PDB-5nni: Dimer structure of Sortilin ectodomain crystal form 2, 3.2 Angstrom Method: X-RAY DIFFRACTION / Resolution: 3.21 Å PDB-5nnj: Dimer structure of Sortilin ectodomain crystal form 3, 4.0 Angstrom Method: X-RAY DIFFRACTION / Resolution: 4.0 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-CA: Unknown entry ChemComp-HOH: WATER ChemComp-CL: Unknown entry
Source	mus musculus (house mouse)
Keywords	PROTEIN TRANSPORT / VPS10 domain family / sorting receptor / ten-bladed beta propeller / 10CC domain / TRANSPORT PROTEIN / VPS10 domain / dimer / acidic pH / transport receptor / internalization / 10 bladed beta-propeller