New study investigates how membrane proteins fold

Researchers at Aston Institute for Membrane Excellence have secured a £439,000 grant from the Leverhulme Trust to investigate one of biology’s most fundamental and poorly understood processes - how membrane proteins fold correctly inside cells.

Membrane proteins are essential for a wide range of cellular functions, including transport and communication across cell membranes. When these proteins misfold, they can lose their function and contribute to serious diseases such as cystic fibrosis, diabetes, Alzheimer’s and Parkinson’s disease.

Despite their importance, the mechanisms governing how these proteins achieve their correct 3D structure remain unclear.

The project, led by Dr Grant Pellowe, will isolate membrane proteins at different stages of folding and analyse their structural transitions using techniques including mass spectrometry and structural spectroscopy. The team will also study how molecular ‘chaperone’ proteins and lipid environments influence the folding process.

The research aims to determine whether folding is primarily encoded in the amino acid sequence itself, or whether cellular conditions play a decisive role in guiding correct protein structure.

“If we can understand how proteins fold correctly inside cells, we can begin to identify where and why this process goes wrong in disease,” said Dr Pellowe. “That knowledge could ultimately help us develop strategies to correct misfolding as proteins are made.”

The findings could also have wider applications in biotechnology, including improving protein design for industrial and pharmaceutical use.

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