Event Overview

The latest webinar in the Instruct-ERIC Structure Meets Function series will be hosted by Instruct Italy on 15th March 2022, 11:00 – 12:00 CET. Register for the webinar here.

Featuring expert speakers from Instruct Centres across Europe, Instruct-ERIC Webinar Series: Structure Meets Function highlights some of the latest developments in structural biology, demonstrating how integrative methods are enabling scientists to decipher the mechanisms that underpin health and disease.

►  Register here.

Moderator: Isabella Felli – CERM, Italy

Talk 1: A Real-Time Approach to Study Cellular Metabolism in Hepatocytes

Speaker: Simone Fjordside

Abstract: An In-Cell NMR Bioreactor allows for real-time metabolomic studies in vitro. Here we intend to establish a robust NMR Bioreactor setup for the study of mammalian liver cells that are encapsulated in a hydrogel with continuous supply of fresh medium. With use of the bioreactor NMR spectra were successfully recorded continuously on living and metabolically active hepatocytes. Due consideration is given to the improvement of cellular viability.

Talk 2: Novel interaction between the key mitochondrial oxidoreductase Mia40 and the major thiol peroxidase Gpx3

Speaker: Kostas Tokatlidis

Abstract: Mitochondrial intermembrane space (IMS) protein biogenesis is critical for mitochondrial function and cell survival. The machinery responsible for the protein biogenesis process in the IMS depends on the critical oxidoreductase Mia40, which under physiological conditions is kept in an active state by the flavoprotein Erv1. We have discovered that under oxidative stress this default pathway is blocked because Erv1 is oxidatively modified and can no longer recycle Mia40 to its active state. Surprisingly, oxidative stress induces an unconventional import mechanism ensuring efficient targeting of the thiol peroxidase Gpx3 into the IMS. Once there, Gpx3 takes over the function of Erv1 and interacts with Mia40 following a novel mechanism that bypasses the blocked Erv1-dependent disulfide relay. This pro-survival mechanism sustains mitochondria fitness against deleterious oxidative damage and illustrates previously unknown links between mitochondria import, redox regulation and mitochondria proteostasis.

Talk 3: Characterization of the intrinsically disordered region of human N-myc downstream regulated gene-1, a possible target for lung cancer therapy

Speaker: Barbara Zambelli, University of Bologna

Abstract: Exposition to carcinogenic nickel compounds activates the cell hypoxia response that up-regulates the hNDRG1 protein. This is a marker that, in lung cancer, is linked to poor prognosis and higher tumor aggressiveness. It contains a non-enzymatic alpha/beta hydrolase globular domain and a unique intrinsically disordered C-terminal sequence, involved in nickel and lipid interactions, and regulated by post-translational phosphorylation.

To understand the role of this protein region in the Ni(II)-driven lung cancer progression, its folding and dynamics, as well as its interaction with Ni(II), were determined using isothermal titration calorimetry, light scattering, circular dichroism and SDSL-EPR. A thorough analysis of the spectroscopic fingerprint of 1H and 13C detected NMR spectra provided detailed information on the effect of pH and Ni(II) binding on the structure. The biophysical data were integrated with the analysis of the Ni(II)-induced expression, subcellular localization and oligomeric states of hNDRG1 in a cell line of lung adenocarcinoma.