Protein Folding

Maurizio Molinari, Group Leader

Riccardo Bernasconi, Elisa Fasana, Carmela Galli Molinari, Jessica Merulla, Julia Noack, Tatiana Soldà

The endoplasmic reticulum (ER) is the site of maturation for proteins destined to the extracellular space, the plasma membrane and to the organelles of the endocytic and secretory pathways. The ER contains molecular chaperones and folding enzymes that assist to attain the native, functional conformation of newly synthesized polypeptides. Mutations, deletions and truncations of the polypeptide chains may cause protein-misfolding diseases characterized by a “loss-of-function” when the mutant protein is degraded or by a “gain-of-toxic-function” when the aberrant polypeptide undergoes aggregation.

The aim of our work is to understand the molecular mechanisms regulating chaperone-assisted protein folding and protein disposal from the mammalian ER. We are also interested in understanding the regulation of chaperone content in the ER lumen. A thorough knowledge of these processes is essential in learning how to intervene in protein biogenesis and how to manipulate protein folding, quality control and degradation to delay progression or even to cure diseases caused by inefficient functioning of the cellular protein factory. It will also increase the efficiency of protocols for ectopic expression of recombinant proteins to be employed in the clinics and in industry.

Projects

• Characterization of Malectin, a Novel ER-Resident Lectin
• Cyclophilins Intervention in Protein Biogenesis and Quality Control in the Mammalian ER
• Disposal of Non-Glycosylated Polypeptides from the Mammalian ER
• E3 Ubiquitin Ligases Regulating Disposal of Membrane-Tethered Misfolded Polypeptides
• ER-Derived Vesicles Involved in ERAD Tuning Are Hijacked for Coronavirus Replication
• Identification of Novel ER-Resident Quality Control Players by “Interactomics”
• Novel Approaches to Inhibit Production and Deposition of the Toxic Aβ Peptide
• Substrate-Specific Mechanisms of Protein Degradation from the ER
• The Selective Clearance of ERAD Regulators from the ER Lumen