Topological characterization of the continuum of allosteric response
arxiv(2024)
摘要
Allosteric regulation in proteins is often accompanied by conformational
changes that facilitate transmission of mechanical signals between distant
ligand binding sites. Typically, these deformations are classified in terms of
specific archetypes, including various types of hinge mechanisms or allosteric
pathways localized to sequences of amino acids.However, many allosteric
deformations resist such strict categorization. Here, we introduce a
quantitative topological description of allosteric deformation, unifying all
archetypal mechanisms into a single framework. The topological description
aligns with two key structural features often associated with allosteric
deformations, namely hinge domains and allosteric pathways, enabling us to
quantify the significance of each of these features. To develop the analysis,
we tune computer-generated mechanical networks to perform allostery-like
functions, obtaining an ensemble of networks that establish a range of possible
allosteric deformations. The analysis shows that these networks' allosteric
mechanisms cannot be described in terms of discrete archetypes - they fall on a
continuum. We then apply the same analysis to a collection of allosteric
proteins with similar results, showing that our framework encompasses these
proteins as well as designed allosteric networks. Our results provide a new
picture for allostery, demonstrating not only how it can be described
quantitatively, but also giving insight into how it emerges as a collective
property.
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