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-Structure paper
タイトル | Acidic Environment Induces Dimerization and Ligand Binding Site Collapse in the Vps10p Domain of Sortilin. |
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ジャーナル・号・ページ | Structure, Vol. 25, Issue 12, Page 1809-11819.e3, Year 2017 |
掲載日 | 2017年12月5日 |
著者 | Dovile Januliene / Jacob Lauwring Andersen / Jeppe Achton Nielsen / Esben Meldgaard Quistgaard / Maria Hansen / Dorthe Strandbygaard / Arne Moeller / Claus Munck Petersen / Peder Madsen / Søren Skou Thirup / |
PubMed 要旨 | 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 ...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. |
リンク | Structure / PubMed:29107483 |
手法 | EM (単粒子) / X線回折 |
解像度 | 3.5 - 13.0 Å |
構造データ | EMDB-3841: PDB-6eho: |
由来 |
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キーワード | PROTEIN BINDING / PROTEIN SORTING RECEPTOR / 10-bladed beta-propeller / Vps10p-D / Endocytosis / Endosome / Glycoprotein / Golgi apparatus / Lysosome / Membrane / Receptor / Transmembrane / SIGNALING PROTEIN |