A multidisciplinary research team from CIC bioGUNE, Biofisika Institute, NIH (National Institutes of Health, USA), BSC (Barcelona Supercomputing Center), and ICVV (Institute of Vine and Wine Sciences) 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 is responsible for transporting and reusing over 60 different proteins.
A common activity in our daily household chores is separating paper, glass, cans, and 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.
The research has been published in Nature Structural & Molecular Biology, one of the most impactful scientific journals in the field of structural and molecular biology.
"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, cans, 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 those found at CIC bioGUNE and BREM (Basque Resource for Electron Microscopy) at the Biofisika Institute, which together have successfully addressed this study.
Reference: Nature Structural & Molecular Biology.
DOI: https://www.nature.com/articles/s41594-023-01014-7
The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.
Ikerbasque - Basque Foundation for Science - is the result of an initiative of the Department of Education of the Basque Government that aims to reinforce the commitment to scientific research by attracting, recovering and consolidating excellent researchers from all over the world. Currently, it is a consolidated organization that has 290 researchers/s, who develop their work in all fields of knowledge.
BRTA is an alliance of 4 collaborative research centres (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 12 technology centres (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Lortek, Neiker, Tecnalia, Tekniker and Vicomtech) with the main objective of developing advanced technological solutions for the Basque corporate fabric.
With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three territories, the alliance seeks to promote collaboration between the research centres, strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness and outspreading the Basque scientific-technological capacity abroad.
BRTA has a workforce of 3,500 professionals, executes 22% of the Basque Country's R&D investment, registers an annual turnover of more than 300 million euros and generates 100 European and international patents per year.
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