Access IBEC scientific production portal (IBEC CRIS), for more detailed information and advanced search features.
Find here the list of all IBEC's publications by year.
by Keyword: Cryo-em
Badia, Marta, Batlle, Cristina, Bolognesi, Benedetta, (2026). Massively parallel quantification of mutational impact on IAPP amyloid formation Nature Communications 17, 4076 
Amyloid fibrils formed by the islet amyloid polypeptide cause pancreatic beta-cell damage, resulting in reduced insulin secretion and type 2 diabetes. Changes in the amino acid sequence of this peptide can influence its aggregation rate, and animals expressing variants that do not form amyloids do not develop type 2 diabetes. Conversely, specific single amino acid changes can accelerate the aggregation rate of this peptide. Here, we employ deep mutational scanning to measure the ability of 1916 islet amyloid polypeptide variants, including substitutions, insertions, truncations and deletions, to nucleate amyloids. Our results identify a continuous stretch of residues from 15 to 32 that is particularly sensitive to mutation. This region, which is likely structured in amyloids, matches the core of the early aggregated species formed by this peptide in vitro. Within this region, mutations in residues 21 to 27 have a substantial effect, suggesting tighter structural constraints. Finally, we compare the mutational atlas of the islet amyloid polypeptide to that of amyloid beta - the peptide that aggregates in Alzheimer's disease - and find that mutations that slow down nucleation correlate between the two amyloids, but mutations that accelerate nucleation in one amyloid cannot be used to predict mutational effects in the other.
JTD Keywords: Aggregation, Amylin gene, Amyloidogenicity, Atomic-resolution structure, Beta, Cryo-em structures, Diabetes-mellitus, Fibril structure, Islet, Polypeptide iapp
Qi, C, Gutierrez, SS, Lavriha, P, Othman, A, Lopez-Pigozzi, D, Bayraktar, E, Schuster, D, Picotti, P, Zamboni, N, Bortolozzi, M, Gervasio, FL, Korkhov, VM, (2023). Structure of the connexin-43 gap junction channel in a putative closed state eLife 12, RP87616
Gap junction channels (GJCs) mediate intercellular communication by connecting two neighbouring cells and enabling direct exchange of ions and small molecules. Cell coupling via connexin-43 (Cx43) GJCs is important in a wide range of cellular processes in health and disease (Churko and Laird, 2013; Liang et al., 2020; Poelzing and Rosenbaum, 2004), yet the structural basis of Cx43 function and regulation has not been determined until now. Here, we describe the structure of a human Cx43 GJC solved by cryo-EM and single particle analysis at 2.26 Å resolution. The pore region of Cx43 GJC features several lipid-like densities per Cx43 monomer, located close to a putative lateral access site at the monomer boundary. We found a previously undescribed conformation on the cytosolic side of the pore, formed by the N-terminal domain and the transmembrane helix 2 of Cx43 and stabilized by a small molecule. Structures of the Cx43 GJC and hemichannels (HCs) in nanodiscs reveal a similar gate arrangement. The features of the Cx43 GJC and HC cryo-EM maps and the channel properties revealed by molecular dynamics simulations suggest that the captured states of Cx43 are consistent with a closed state.© 2023, Qi, Acosta Gutierrez et al.
JTD Keywords: cryo-em, dehydroepiandrosterone dhea, expression, gap junction channel, gene, gja1 mutations, hemichannel, membrane protein, phenotype, protein, structure, system, visualization, Biochemistry, Chemical biology, Connexin-43, Cryo-em, Gap junction channel, Hemichannel, Human, Membrane protein, Molecular biophysics, Oculodentodigital dysplasia, Structural biology, Structure
