6EHO
Dimer of the Sortilin Vps10p domain at low pH
Summary for 6EHO
| Entry DOI | 10.2210/pdb6eho/pdb |
| Descriptor | Sortilin, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | protein sorting receptor, 10-bladed beta-propeller, vps10p-d, endocytosis, endosome, glycoprotein, golgi apparatus, lysosome, membrane, receptor, transmembrane, signaling protein, protein binding |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 82302.56 |
| Authors | Thirup, S.S.,Quistgaard, E.H.,Januliene, D.,Andersen, J.L.,Nielsen, J.A. (deposition date: 2017-09-14, release date: 2017-12-06, Last modification date: 2024-01-17) |
| Primary citation | Januliene, D.,Andersen, J.L.,Nielsen, J.A.,Quistgaard, E.M.,Hansen, M.,Strandbygaard, D.,Moeller, A.,Petersen, C.M.,Madsen, P.,Thirup, S.S. Acidic Environment Induces Dimerization and Ligand Binding Site Collapse in the Vps10p Domain of Sortilin. Structure, 25:1809-1819.e3, 2017 Cited by PubMed Abstract: Sortilin is a neuronal receptor involved in transmembrane signaling, endocytosis, and intracellular sorting of proteins. It cycles through a number of cellular compartments where it encounters various acidic conditions. The crystal structure of the sortilin ectodomain has previously been determined at neutral pH. Here, we present the 3.5-Å resolution crystal structure of sortilin at pH 5.5, which represents an environment similar to that of late endosomes, where ligands are released. The structure reveals an overall distortion of the 10-bladed β-propeller domain. This distortion and specific conformational changes, caused by protonation of a number of histidine residues, render the currently known binding sites unavailable for ligand binding. Access to the binding sites is furthermore blocked by a reversible and pH-dependent formation of tight sortilin dimers, also confirmed by electron microscopy, size-exclusion chromatography, and mutational studies. This study reveals how sortilin binding sites are disrupted and explains pH-dependent ligand affinity. PubMed: 29107483DOI: 10.1016/j.str.2017.09.015 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.5 Å) |
Structure validation
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