The Levinthal paradox of the interactome |
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Authors: | Tompa Peter Rose George D |
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Institution: | VIB Department of Structural Biology, Vrije Universiteit Brussel, Brussels, Belgium. ptompa@vub.ac.be |
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Abstract: | The central biological question of the 21st century is: how does a viable cell emerge from the bewildering combinatorial complexity of its molecular components? Here, we estimate the combinatorics of self-assembling the protein constituents of a yeast cell, a number so vast that the functional interactome could only have emerged by iterative hierarchic assembly of its component sub-assemblies. A protein can undergo both reversible denaturation and hierarchic self-assembly spontaneously, but a functioning interactome must expend energy to achieve viability. Consequently, it is implausible that a completely “denatured” cell could be reversibly renatured spontaneously, like a protein. Instead, new cells are generated by the division of pre-existing cells, an unbroken chain of renewal tracking back through contingent conditions and evolving responses to the origin of life on the prebiotic earth. We surmise that this non-deterministic temporal continuum could not be reconstructed de novo under present conditions. |
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Keywords: | interactome protein–protein interaction Levinthal protein folding irreversibility assembly pathway steady state combinatorics |
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