title: Retinol and retinol-binding protein stabilize transthyretin via formation of retinol transport complex.
abstract: Transthyretin (TTR) is a plasma hormone carrier protein associated with hereditary and senile forms of systemic amyloid disease, wherein slow tetramer disassembly is thought to be an obligatory step. Plasma transport of retinol is carried out exclusively by the retinol-binding protein (RBP), through complexation with transthyretin. Using mass spectrometry to examine the subunit exchange dynamics, we find that retinol stabilizes the quaternary structure of transthyretin, through its interactions with RBP, reducing the rate of transthyretin disassembly ∼17-fold compared to apoTTR. In the absence of retinol but in the presence of RBP, transthyretin is only marginally stabilized with the rate of disassembly reduced ∼two-fold with respect to apoTTR. Surprisingly, we found two retinoids that stabilize transthyretin directly, in the absence of RBP, whereas retinol itself requires RBP in order to stabilize transthyretin. Our results demonstrate new roles for RBP and retinoids as stabilizers of transthyretin.
authors.affiliation: Department of Chemistry, Oxford University, United Kingdom.
authors.forename: Suk-Joon
authors.initials: SJ
authors.lastname: Hyung
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Deroo
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
mesh_terms: D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011228:Prealbumin / Q000737:chemistry*; D011485:Protein Binding; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D014801:Vitamin A / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011228:Prealbumin; D021122:Protein Subunits; D012177:Retinol-Binding Proteins; D014801:Vitamin A