Curator

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Prof. Dr. Franz-Ulrich Hartl

Phone:+49 89 8578-2244Fax:+49 89 8578-2211

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Cell Biology . Developmental Biology . Genetics . Immunobiology . Neurosciences . Structural Biology

Protein folding

Proteins are chain-like molecules. In order to function properly, they must fold into complex three-dimensional shapes. The failure of proteins to fold properly has been linked to various diseases, including cancer, Huntington’s disease and Alzheimer’s disease. Understanding protein folding will aid the development of therapies that remove or prevent the formation of misfolded protein clumps.
Fig. 1: X-ray crystallographic characterization of a three-dimensionally folded maltose-binding protein. Zoom Image
Fig. 1: X-ray crystallographic characterization of a three-dimensionally folded maltose-binding protein.

Proteins perform vital cellular functions; however, in order to work, these chain-like molecules must fold into complex, three-dimensional structures1 (Fig.1). The process is quality controlled by complex molecules within the cell2,3; however, it can go awry, yielding misfolded proteins that clump into toxic aggregates (Fig. 2). Many age-related diseases, such as Alzheimer’s disease, are thought to be caused by the build-up of these aggregates4,5. A co-ordinated network of interdisciplinary research is developing therapies that aim to remove or prevent the build-up of these misfolded proteins. If successful, their potential to improve quality of life is immense.

PROTEIN ORIGAMI

Proteins are the workhorses of the cell: they are essential molecules that fulfil vital and diverse cellular functions, such as catalysing chemical reactions, providing structural support, and mediating cell signalling and development. Human cells contain thousands of proteins, each consisting of a chain of 100–500 amino-acid building blocks. In order to work, however, these newly built proteins must first fold into a complex yet highly specific three-dimensional shape.

<b>Fig. 2 | Schematic representation of protein folding.</b> Zoom Image
Fig. 2 | Schematic representation of protein folding.

With hundreds of thousands of different possible structures for each protein, achieving the correct one is a tall order; yet, most proteins manage to perform this task quickly and efficiently. Larger proteins tackle the problem by folding different parts of the molecule separately. The process is driven by hydrophobic and hydrophilic properties of amino acids in different sections of the protein. Water-repelling amino acids interact with one other to build a hydrophobic core, whereas water-attracting amino acids settle on the exterior of the protein. This causes the protein chain to collapse into a globular structure that forms a stable, three-dimensional, biologically active protein.

 
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