Protein Knots Gain New Evolutionary Significance

Protein Knots Gain New Evolutionary Significance

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A new study suggests that protein knots, a structure whose formation remains a mystery, may have specific functional advantages that depend on the nature of the protein’s architecture. Relatively little is known about protein folding, the process by which a polypeptide chain with a specific sequence of amino acid chains forms the three-dimensional structures — their “native states” — required to become functional. How this process reproducibly achieves the required structure is the subject of intensive study. Even harder is understanding how this is accomplished for knotted proteins, where the chain loops around itself in entanglements of varying complexity; or the even rarer slipknotted proteins, where a loop is bound by another segment of the protein chain, similar to a shoelace bow.

“From an evolutionary point of view, knotting might seem unlikely to occur but, in fact, it does occur,” said co-author Kenneth Millett, a professor of mathematics at UC Santa Barbara. The researchers, who published their work in Proceedings of the National Academy of Sciences, found that protein knots and slipknots, instead of being discarded through the process of evolution, are often strongly conserved. This suggests that, despite their reduced efficiency of folding, the knots are somehow advantageous and important to the function of the protein.

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