Publications

Hereditary hemochromatosis (HH) is an iron metabolism disease clinically characterized by excessive iron deposition in parenchymal organs such as liver, heart, pancreas, and joints. It is caused by mutations in at least five different genes. HFE hemochromatosis is the most common type of hemochromatosis, while non-HFE related hemochromatosis are rare cases. Here, we describe six new patients of non-HFE related HH from five different families. Two families (Family 1 and 2) have novel nonsense mutations in the HFE2 gene have novel nonsense mutations (p.Arg63Ter and Asp36ThrfsTer96). In this new collaborative article led by Mayka Sánchez from the Department of Basic Sciences at UIC Barcelona, our lab gave the structural context for the effect of the identified mutations in TFR2 interactions.

Comparative modeling of the TFR2 dimer complexed with TF. (A) TFR2 chains are shown in cyan and pink, while TF chains are shown in green and orange. Dimeric interactions between TFR2 chains, close to Asp680 position (red circle at the α-15 helix, pink chain), are made between residues in the α-18 helix of one TFR2 chain (pink chain) and the loop located between the β-6 and β-7 strands of the other (cyan chain). (B) Sequence alignment of the TFR1 and TFR2 proteins near the TFR2 680 position (green arrow). Numbering is according to the TFR1 sequence, and the secondary structure depiction is based on the TFR1 structure (PDB ID 1CX8). The alignment coloring was produced by the ESPript 3.0 web server [40], where position with red background means absolute sequence conservation. (C–E) Structural context of positions TFR1-Asp648 (C, purple), TFR2-Asp680 (D, pink), and TFR2-Asp680Tyr (E, magenta). Residue names of TFR1/2 appear in white, while residues in TF are in black. Significant interactions are shown with dashed lines.

Hernández, G.; Ferrer-Cortès, X.; Venturi, V.; Musri, M.; Pilquil, M.F.; Torres, P.M.M.; Rodríguez, I.H.; Mínguez, M.À.R.; Kelleher, N.J.; Pelucchi, S.; Piperno, A.; Alberca, E.P.; Ricós, G.G.; Giró, E.C.; Pérez-Montero, S.; Tornador, C.; Villà-Freixa, J.; Sánchez, M. New Mutations in HFE2 and TFR2 Genes Causing Non HFE-Related Hereditary Hemochromatosis. Genes 2021, 12, 1980. https://doi.org/10.3390/genes12121980

The CBBL has completed part of the work of a three years long project on translational bioinformatics in cystic fibrosis (Activa). Our main role in the project was the determination of a model structure for CFTR, the chloride channel whose mutations are in the basis of the disease, as well as being a target for acute watery diarrhea drugs.

The new model, built in collaboration with Nir Ben-Tal’s lab at Tel Aviv University, proposes an open conformation of the channel, oposite to previous models, paving the way for the development of new drugs for both activation and blocking of the channel.