Crystal structure of the ligand-free form of the Vps10 ectodomain of dimerized Sortilin at acidic pH.
FEBS Lett
; 592(15): 2647-2657, 2018 08.
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| ID: mdl-29972886
ABSTRACT
Sortilin is a multifunctional sorting receptor involved in cytokine production in immune cells. To understand the mechanism of Sortilin-mediated cytokine trafficking, we determined the 2.45-Å structure of the dimerized Sortilin ectodomain (sSortilin or the Vps10-domain) crystallized at acidic pH. Substantial conformational changes upon dimerization lead to the intermolecular hydrophobic interaction between the conserved E455 and F137. Analysis of the electrostatic surface and size-exclusion chromatography revealed that sSortilin dimerization occurs due to an increase in hydrophobic interactions at the neutral dimer interface at acidic pH. The N682-attached N-glycan in the vicinity of the dimer interface implies its involvement in the dimerization. The disruption of Sortilin dimerization by mutations impairs efficient interferon-alpha secretion from cells. These results suggest the functional importance of Sortilin dimerization in cytokine trafficking.
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MEDLINE
Asunto principal:
Proteínas Adaptadoras del Transporte Vesicular
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Dominios y Motivos de Interacción de Proteínas
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Multimerización de Proteína
Idioma:
En
Revista:
FEBS Lett
Año:
2018
Tipo del documento:
Article