9I0N
Cryo-EM structure of human sortilin ectodomain
Summary for 9I0N
| Entry DOI | 10.2210/pdb9i0n/pdb |
| EMDB information | 52562 |
| Descriptor | Sortilin, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | trafficking, vacuolar protein sorting, vps10, beta propeller, neurotensin binding receptor 3, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 84010.58 |
| Authors | Boniardi, I.,Coscia, F. (deposition date: 2025-01-15, release date: 2025-12-17, Last modification date: 2026-07-01) |
| Primary citation | Boniardi, I.,Tanzi, G.,Di Ianni, A.,Graziadei, A.,Nedeljkovic, M.,Stejskalova, C.,Coscia, F. Molecular recognition of thyroglobulin by sortilin. Nat Commun, 17:-, 2026 Cited by PubMed Abstract: Sortilin is a ubiquitous membrane receptor mediating trafficking of protein cargoes. In the thyroid, sortilin binds thyroglobulin (TG) during its endocytosis, a key process in thyroid homeostasis. Although sortilin has been proposed to recognise highly iodinated TG, the molecular details of this interaction remain unknown. In this work, using an integrative structural biology approach, we reveal that sortilin binds an unstructured TG C-terminal peptide and exhibits a strong preference for the monomeric TG over the commonly known dimeric form. We find that sortilin-TG interaction is independent of the iodination state of TG and instead relies on the conversion to its monomeric state, presumably promoted by extracellular degradation. Furthermore, using AlphaPulldown and sequence analysis, we show that recognition of other reported ligands by sortilin likely relies on similar unstructured peptide motifs, which are not constrained to a single binding orientation within the receptor cavity. Overall, this study reveals the TG-sortilin binding interface and provides insights into the recognition mechanism of other cargoes by sortilin. PubMed: 41580413DOI: 10.1038/s41467-026-68658-z PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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