Month: September 2022

SELECTION FOR FUNCTIONALITY. “McConkey predicted that most cellular proteins interact extensively and transiently with other macromolecules to produce a functional ‘quinary’ structure that constrains protein evolution by accommodating only those mutations with no functional implications, i.e. noninteracting sites.” http://onlinelibrary.wiley.com/doi/10.1111/febs.13744/full View in LinkedIn

RESISTANCE TO NEW IDEAS. “Despite strong evidence to support the abundance of functional macromolecular assemblies in vivo, biochemistry developed mainly from the view that cells were membrane-enclosed bags of homogenous cytosol in which polymers and metabolites diffused randomly to interact with each other.” http://onlinelibrary.wiley.com/doi/10.1111/febs.13744/full View in LinkedIn

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OLD BIOCHEMICAL CONCEPT. “The lack of order in this ‘random’ cytoplasm led to the idea that it was unnecessary to study protein behaviour in the context of the intracellular environment.” http://onlinelibrary.wiley.com/doi/10.1111/febs.13744/full View in LinkedIn

IN VITRO. “Buffered aqueous solutions became the preferred milieu for the characterisation of pure proteins. Thus, biochemistry tended towards reductionist studies focused on a single macromolecule in ideal solutions.” http://onlinelibrary.wiley.com/doi/10.1111/febs.13744/full View in LinkedIn

MACROMOLECULAR ASSEMBLIES. “An early demonstration of the autonomous, modular and cooperative nature of functional assemblies or ‘protein machines’ was made by Alberts who presented the DNA replication apparatus (comprising > 40 proteins).” http://onlinelibrary.wiley.com/doi/10.1111/febs.13744/full View in LinkedIn

MOLECULAR MACHINES. “Alberts urged biochemists to ‘think of molecular genetics in terms of “protein machines” rather than in terms of sequential reactions that are carried out by individual proteins’. This provocative insight emphasised the need for ordered, sophisticated machinery in complex living systems, thus ‘freeing the biological process from the necessity of relying on random motions’.” http://onlinelibrary.wiley.com/doi/10.1111/febs.13744/full View in LinkedIn

STRUCTURED PROXIMITY. “The spatiotemporal clustering of functionally related macromolecules increases the probability and rate of productive encounters. The enhanced specificity afforded by the cooperative interactions of multicomponent protein machines resolved questions of how weak, moderately specific interactions (e.g. transcription factor-DNA binding) became functional in vivo.” http://onlinelibrary.wiley.com/doi/10.1111/febs.13744/full View in LinkedIn

CONFIRMED. “In the past 20 years, the ubiquity of macromolecular machines has been demonstrated.” http://onlinelibrary.wiley.com/doi/10.1111/febs.13744/full View in LinkedIn

MOLECULAR ECOSYSTEMS. “Molecular sociology in the cell is dominated by transient, quinary interactions that link and extend machines to produce functional molecular communities or hyperstructures.” http://onlinelibrary.wiley.com/doi/10.1111/febs.13744/full View in LinkedIn