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3D reconstruction of the ESCPE-1 coat (heterodimeric combinations of SNX protein family).
Cerdanyola del Vallès, 19th January 2024 A work published in the journal Nature Structural & Molecular Biology has concluded that proteins that need to be recycled coordinate their own "selective collection". The study is the result of an international collaboration of scientist from CIC bioGUNE, Biofisika Institute, NIH (National Institutes of Health, USA), BSC (Barcelona Supercomputing Center) and ICVV (Institute of Vine and Wine Sciences).
Using synchrotron light at XALOC beamline of ALBA (among other techniques), the research team has revealed the structure of one of the cellular machineries for protein recycling. This machinery is known as ESCPE-1 (Endosomal Sorting Complex Promoting Exit 1) and its function is to transport and reuse over 60 different proteins. Understanding the protein recycling process inside cells is crucial for designing mechanisms to correct errors that lead to inefficient recycling or improper localization of proteins within the cell.
A common activity in our daily household chores is separating paper, glass or plastic to deposit them in the appropriate containers. Through recycling, we can reduce resource consumption, save energy, and minimize waste. Similarly, our cells recycle many of their components to achieve the same benefits.
"Many of the proteins transported and reused by this cellular machinery for protein recycling are cell receptors involved in cell growth and proliferation, and they appear dysregulated in different types of cancer. In this study, we have revealed the organization of ESCPE-1 at the atomic level and how the receptors to be recycled contribute to their own transport. Going back to the analogy of paper, glass and plastic, it is like discovering the mechanism of selective collection for one of these containers." explains Aitor Hierro, Ikerbasque lead researcher from the “Membrane Trafficking Lab” at CIC bioGUNE.
Conceptually, the study provides a very simple yet fundamental idea. Proteins that need to be recycled coordinate their own selective collection. "Our cells use and reuse many of their components by efficiently managing their localization and availability. Understanding these processes at the atomic level is essential for designing mechanisms that can correct management errors where some proteins are not efficiently recycled or end up in cellular locations where they do not belong, as occurs in some types of cancer and certain neurodegenerative diseases," says Aitor Hierro.
The work, which has been carried out over the past five years, has utilized two of the most relevant techniques in structural biology: X-ray crystallography and cryo-electron microscopy. Both techniques require large infrastructures like ALBA, the BREM (Basque Resource for Electron Microscopy) at the Biofisika Institute in Bilbao, and the eBIC (electron Bio-Imaging Centre) in UK which together have successfully addressed this study.
