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[PMID]: | 28827148 |
[Au] Autor: | Januliene D; Manavalan A; Ovesen PL; Pedersen KM; Thirup S; Nykjær A; Moeller A |
[Ad] Endereço: | Department of Structural Biology, Max Planck Institute of Biophysics, Max-von-Laue-Straße 3, 60438 Frankfurt am Main, Germany; DANDRITE, iNANO, Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark. |
[Ti] Título: | Hidden Twins: SorCS Neuroreceptors Form Stable Dimers. |
[So] Source: | J Mol Biol;429(19):2907-2917, 2017 Sep 15. | [Is] ISSN: | 1089-8638 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | SorCS1, SorCS2 and SorCS3 belong to the Vps10p-domain family of multiligand receptors. Genetic and functional studies have linked SorCS receptors to psychiatric disorders, Alzheimer's disease and type 2 diabetes, demonstrating critical roles in neuronal functionality and metabolic control. Surprisingly, their structural composition has so far not been studied. Here we have characterized SorCS1, SorCS2 and SorCS3 using biochemical methods and electron microscopy. We found that their purified extracellular domains co-exist in stable dimeric and monomeric populations. This was supported by co-immunoprecipitation experiments, where membrane-bound dimers were successfully pulled down from cell lysate. While dimers were virtually unbreakable, dimerization of the monomeric population was promoted through enzymatic deglycosylation. We conclude that post-translational modifications, specifically the degree and pattern of glycosylation, regulate the oligomeric state of the protein. Hence, cells may dictate ligand specificity by controlling the ratio between monomers and dimers and, therefore, regulate the multiple functions of SorCS receptors. |
[Mh] Termos MeSH primário: |
Multimerização Proteica Receptores de Superfície Celular/química Receptores de Superfície Celular/metabolismo Receptores de Neuropeptídeos/química Receptores de Neuropeptídeos/metabolismo
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[Mh] Termos MeSH secundário: |
Imunoprecipitação Microscopia Eletrônica Processamento de Proteína Pós-Traducional
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Receptors, Cell Surface); 0 (Receptors, Neuropeptide); 0 (SORCS1 protein, human); 0 (SORCS2 protein, human); 0 (SorCS3 protein, human) |
[Em] Mês de entrada: | 1710 |
[Cu] Atualização por classe: | 171002 |
[Lr] Data última revisão:
| 171002 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170823 |
[St] Status: | MEDLINE |
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