Key enzyme helps fungi deal with misfolded proteins

Proteins need to fold correctly in order to function. When this does not happen, the cell needs to be able to identify and break down misfolded proteins before they cause problems. A new study from SLU shows that filamentous fungi use a different solution for this quality-control process than what has previously been known from, for example, yeasts and animals.

The researchers studied the mould Neurospora crassa and focused on the process in which sugar chains are removed from misfolded proteins before they are broken down. The study shows that the enzyme GH18-10 plays a central role in this process. In many organisms, the enzyme PNGase helps deal with proteins that do not function properly. In filamentous fungi, however, this enzyme appears to have lost that function.

An enzyme with an unexpectedly important role

Instead, the enzyme GH18-10 appears to take over an important part of the job.

– When we looked at different enzymes in Neurospora crassa, we saw that GH18-10 was able to remove sugar chains from proteins and help break down proteins that had become misfolded, says Anastasios Samaras.

– What is interesting is that fungi seem to have evolved alternative ways of solving a very basic problem in the cell: what to do with proteins that do not fold correctly. Our results show how evolution can find alternative solutions when a mechanism that is common in other organisms has changed or lost its enzymatic function, says Georgios Tzelepis.

When the researchers removed the gene encoding GH18-10, the fungus was affected in several ways. Gene expression changed significantly, its response to different types of stress was altered, and the fungus also had major problems with sexual reproduction.

This suggests that the enzyme plays a more central role in the fungus’s basic functions than previously understood.

Important for fungi’s ability to function under stress

Filamentous fungi produce and secrete large amounts of proteins, including enzymes that help them break down material in their surroundings. For this to work, they need an effective system for controlling protein quality.

The study also shows that the fungus can activate alternative mechanisms when the usual process is disrupted. Under stress affecting the cell’s protein-handling system, the activity of another gene encoding an enzyme involved in processing sugar molecules also increased.

– Filamentous fungi need to be able to produce, process and secrete large amounts of proteins. That is why it is important to understand how the fungus makes sure that its proteins are of the right quality. When we disrupted this process, we saw effects ranging from which genes are active and how the fungus responds to stress, to its ability to reproduce, says Magnus Karlsson.

The results therefore provide new knowledge about how filamentous fungi maintain cellular balance and adapt when exposed to stress.

Basic knowledge with implications for fungal applications

Filamentous fungi play an important role both in nature and in industry. They are particularly interesting because they can produce and secrete large amounts of proteins and enzymes, which can be used in various biotechnological processes. However, we still know relatively little about how fungi deal with proteins that do not fold correctly. By investigating this process, the study provides new knowledge about how fungi function and respond to stress.

– To understand how filamentous fungi function, we also need to understand what happens inside their cells. This study gives us another piece of the puzzle when it comes to how fungi keep their proteins in balance and adapt when the system is under stress, concludes Georgios Tzelepis.

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The study has been published in The FEBS Journal.

Read the full article here: https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.70666