New Insights Into Initial Protein Synthesis Stages

Researchers discover protein complex NAC plays key role in early protein folding process

Mar. 24, 2026 at 4:00am

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An international research team led by scientists from the Center for Molecular Biology of Heidelberg University has found that the protein complex NAC performs an essential task in the earliest phase of creating human proteins by starting the first steps towards folding proteins into their correct three-dimensional structures. The researchers discovered that NAC binds to the nascent protein building-blocks formed by the ribosome and initiates the folding that is essential for functional proteins.

Why it matters

This discovery provides new insights not only on protein synthesis but also on cellular strategies to avoid incorrect protein folding, which can lead to serious illnesses like neurodegenerative diseases. Understanding the role of NAC in the early stages of protein folding could help researchers develop treatments for diseases caused by protein misfolding.

The details

The NAC complex binds to the ribosome, the cells' protein factory, where it coordinates the different steps to make proteins. The researchers found that NAC binds to a large fraction of all nascent proteins produced in a human cell, inducing the correct folding of proteins through this interaction and preventing incomplete intermediate products from leading to incorrect folding. Using cryo-electron microscopy, the team revealed how NAC has a binding site facing the ribosomal tunnel that is designed for specific areas in the nascent proteins. An artificial variant of NAC without this binding site was no longer able to fulfill its folding function.

  • The research studies were conducted in the context of the ERC Synergy consortium "Mechanisms of co-translational assembly of multi-protein complexes".

The players

Center for Molecular Biology of Heidelberg University

The research team that led the discovery of NAC's role in early protein folding is based at this university research center.

Prof. Dr Bernd Bukau

The molecular biologist who heads the "Biogenesis and Quality Control of Proteins" research group at the Center for Molecular Biology of Heidelberg University and coordinated the ERC Synergy consortium.

Dr Günter Kramer

The head of the ZMBH group "Cotranslational Protein Maturation" who collaborated on the project.

Prof. Dr Sander Tans

The researcher at AMOLF, a research institute for the physics of functional complex matter in Amsterdam, who participated in the joint ERC Synergy project.

Prof. Dr Nenad Ban

The researcher at ETH Zurich who participated in the joint ERC Synergy project.

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What they’re saying

“Researchers have long known that the NAC complex intervenes in different ways in the various processes of protein synthesis and plays an important role as a molecular control center. With our results we can add a further piece of the puzzle to the still incomplete picture.”

— Dr Günter Kramer, Head of the ZMBH group "Cotranslational Protein Maturation"

“At the same time, NAC prevents incomplete intermediate products from leading to incorrect folding.”

— Prof. Dr Bernd Bukau, Head of the "Biogenesis and Quality Control of Proteins" research group at the Center for Molecular Biology of Heidelberg University

The takeaway

This discovery of NAC's role in the early stages of protein folding provides important insights that could help researchers better understand and potentially treat diseases caused by protein misfolding, such as neurodegenerative disorders.