10.1021/cb100144v.s001
Suk-Joon Hyung
Suk-Joon
Hyung
Stéphanie Deroo
Stéphanie
Deroo
Carol V. Robinson
Carol V.
Robinson
Retinol and Retinol-Binding Protein Stabilize Transthyretin <i>via</i> Formation of Retinol Transport Complex
American Chemical Society
2010
tetramer disassembly
amyloid disease
mass spectrometry
transthyretin
TTR
Plasma transport
subunit exchange dynamics
RBP
plasma hormone carrier protein
retinol
Retinol Transport ComplexTransthyretin
quaternary structure
2010-12-17 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Retinol_and_Retinol_Binding_Protein_Stabilize_Transthyretin_i_via_i_Formation_of_Retinol_Transport_Complex/2703745
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.