Slurps.

An unusual and relevant protein structure.


A recent paper [BBC coverage] regarding work conducted at the MRC centre for human reproductive health in Edinburgh has revealed a role suggested a role for the proteoglycan Decorin in prostate cancer. The paper describes observational work looking at the presence and production of 5 proteins (including Decorin), and their distribution within different cell layers in the developing rat prostate. Looking at differential expression of Decorin during prostate development is an entirely reasonable thing to, given Decorin’s previously hypothesised role in organogenesis (development of organs) and tissue differentiation [REF].

In the recent paper, Henke et al also show that levels of Decorin are often significantly reduced in prostate cancer, and this is suggestive that Decorin might be a tumour suppressor gene – i.e. remove Decorin, and you may remove a barrier that prevents normal cells from becoming cancerous. Potential mechanisms are discussed in the paper, and it seems entirely plausible that decorin might function in this way – its role in organogenesis requires that it regulate cell division in some way – failure of this regulation of this might result in unchecked cell division – i.e. cancer.

Anyway, this all served to remind me of the small leucine rich repeat proteoglycans, or SLRPs – pronounced, ‘slurps’.

Decorin was the first SLRP (of the 17 known in the human genome) to have its structure determined [ PDBe | Pubmed ], by Jordi Bella and Paul Bishop, working at the University of Manchester (disclosure: I work there now).

SLRPs are pretty unusual looking structures – officially their fold is called a “beta-alpha-right-handed-superhelix”, and it looks a little something like this:

Each leucine rich repeat forms a single helical turn of the “beta-alpha-right handed superhelix” – the hydrophobic (water-hating) leucine residues form a continuous beta sheet (the rainbow coloured arrows in the figure below) which makes up the concave face of the protein. The convex face of the protein is made up of hydrophilic (water loving) loops.

The fact that this large concave hydrophobic face exists and is exposed to solvent is energetically unfavourable – however, in both the crystal structure, and in solution, Decorin exists as a dimer (2 Decorin molecules non-covalently bound to each other), and formation of this dimer hides this hydrophobic concave face from the solvent, making it thermodynamically more favourable.

Hopefully it is clear in the above figure that the concave faces of the protein are packed against each other, preventing them from having to interact with solvent.

It’s a neat example of how the primary (amino acid sequence – in this case rich in hydrophobic leucine residues), secondary (beta-strands) and tertiary (beta-sheet) structure of a protein influences its quaternary structure – in this case its oligomeric state.

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