Structure of the N-terminal segment of human retinol dehydrogenase 11 and its preferential lipid binding using model membranes

Abstract

Retinol dehydrogenase 11 (RDH11) has been postulated to be anchored to membranes by means of its N-terminal segment in retinal pigment epithelial (RPE) cells where it participates to the visual cycle. The analysis of the primary sequence of RDH11 revealed that its N-terminal hydrophobic segment could be involved in the anchoring of this enzyme to membranes. However, no information is yet available on the properties of this N-terminal segment to support this role. The secondary structure and membrane binding of two N-terminal peptides of RDH11 with different lengths have thus been investigated to provide this information. Online tools allowed predicting an α-helical secondary structure for both peptides. Infrared spectroscopy and circular dichroism have shown that the α-helix of the Long-peptide (35 amino acids) is longer and more rigid than that of the Short-peptide (25 amino acids) regardless of the type of solvent. Langmuir monolayers have been used as a model membrane to study lipid-peptide interactions. Values of maximum insertion pressure and synergy suggested a preferential binding of the Long-peptide to lipids with a phosphoethanolamine polar head group, which are abundant in the RPE. Furthermore, infrared spectroscopy in monolayers has shown that the α-helical structure of the Long-peptide is more stable in the presence of saturated phospholipids whereas the structure of the Short-peptide is mainly disordered. Altogether, the present data demonstrate that the α-helical hydrophobic core of the N-terminal segment of RDH11 displays properties typical of transmembrane domains, in agreement with its postulated role in the membrane anchoring of this protein.

The molecular aspects of absorption and metabolism of carotenoids and retinoids in vertebrates

“…The N-terminal residues are essential for the membrane localization and topology of this enzyme, whereas the C-terminus was postulated to be involved in the stabilization of the protein's membrane orientation. A similar role for the N-terminal segment was postulated for RDH11 [150,151]. Contrary to these models, the presence of endoglycosidase H-sensitive N-linked sugar oligosaccharides on RDH12 suggest a luminal orientation for this enzyme [152].…”

Mesoporous Non-stacked Graphene-receptor Sensor for Detecting Nerve Agents

“…The hydrophobicity could also demonstrate that the HFHPB moiety was successfully grafted to NSrGO 33 34 . The hydrophobicity of NSrGO-HFHPB was confirmed by water contact angle (WCA) measurements as shown in Fig.…”

The interaction of selenoprotein F (SELENOF) with retinol dehydrogenase 11 (RDH11) implied a role of SELENOF in vitamin A metabolism

“…RDH11 belongs to the short-chain dehydrogenases/reductases (SDR) family [ 16 ] and exhibits more efficient enzyme activity for reduction of all-trans-retinaldehyde than oxidation of all-trans-retinol (vitamin A, VA) [ 23 ]. The results of this study verify this, and detect that over expressed SELENOF inhibits the exogenous RDH11 retinal reductase activity, suggesting that SELENOF is possibly involved in VA metabolism.…”

“…Human retinol dehydrogenase 11 RDH11 belongs to the short-chain dehydrogenases/ reductases (SDR) family [ 16 ]. It is able to reduce both all-trans- and cis-retinaldehydes into all- trans- and cis- retinol (Vitamin A) [ 17 , 18 ].…”