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Console L, Tolomeo M, Cosco J, et al. Impact of natural mutations on the riboflavin transporter 2 and their relevance to human riboflavin transporter deficiency 2. IUBMB Life. 2021;doi: 10.1002/iub.2541.
Console, L., Tolomeo, M., Cosco, J., Massey, K., Barile, M., & Indiveri, C. (2021). Impact of natural mutations on the riboflavin transporter 2 and their relevance to human riboflavin transporter deficiency 2. IUBMB life, . https://doi.org/10.1002/iub.2541
Console, Lara, et al. "Impact of natural mutations on the riboflavin transporter 2 and their relevance to human riboflavin transporter deficiency 2." IUBMB life vol. (2021). doi: https://doi.org/10.1002/iub.2541
Console L, Tolomeo M, Cosco J, Massey K, Barile M, Indiveri C. Impact of natural mutations on the riboflavin transporter 2 and their relevance to human riboflavin transporter deficiency 2. IUBMB Life. 2021 Aug 24; doi: 10.1002/iub.2541. Epub 2021 Aug 24. PMID: 34428344.
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IUBMB Life. 2021 Aug 24; doi: 10.1002/iub.2541. Epub 2021 Aug 24.

Impact of natural mutations on the riboflavin transporter 2 and their relevance to human riboflavin transporter deficiency 2.

IUBMB life

Lara Console, Maria Tolomeo, Jessica Cosco, Keith Massey, Maria Barile, Cesare Indiveri

Affiliations

  1. Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Arcavacata di Rende, Italy.
  2. Department of Biosciences, Biotechnology, and Biopharmaceutics, University of Bari, Bari, Italy.
  3. Cure RTD Foundation, Calgary, Alberta, Canada.

PMID: 34428344 DOI: 10.1002/iub.2541

Abstract

Riboflavin transporter deficiency 2 (RTD2) is a rare neurological disorder caused by mutations in the Solute carrier family 52 member 2 (Slc52a2) gene encoding human riboflavin transporter 2 (RFVT2). This transporter is ubiquitously expressed and mediates tissue distribution of riboflavin, a water-soluble vitamin that, after conversion into FMN and FAD, plays pivotal roles in carbohydrate, protein, and lipid metabolism. The 3D structure of RFVT2 has been constructed by homology modeling using three different templates that are equilibrative nucleoside transporter 1 (ENT1), Fucose: proton symporter, and glucose transporter type 5 (GLUT5). The structure has been validated by several approaches. All known point mutations of RFVT2, associated with RTD2, have been localized in the protein 3D model. Six of these mutations have been introduced in the recombinant protein for functional characterization. The mutants W31S, S52F, S128L, L312P, C325G, and M423V have been expressed in E. coli, purified, and reconstituted into proteoliposomes for transport assay. All the mutants showed impairment of function. The K

© 2021 International Union of Biochemistry and Molecular Biology.

Keywords: gene variants; proteoliposomes; rare diseases; riboflavin; structure-function relationship; transport proteins

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