Hot spots for allosteric regulation on protein surfaces

Kimberly A. Reynolds, Richard N. McLaughlin, Rama Ranganathan

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

Recent work indicates a general architecture for proteins in which sparse networks of physically contiguous and coevolving amino acids underlie basic aspects of structure and function. These networks, termed sectors, are spatially organized such that active sites are linked to many surface sites distributed throughout the structure. Using the metabolic enzyme dihydrofolate reductase as a model system, we show that: (1) the sector is strongly correlated to a network of residues undergoing millisecond conformational fluctuations associated with enzyme catalysis, and (2) sector-connected surface sites are statistically preferred locations for the emergence of allosteric control in vivo. Thus, sectors represent an evolutionarily conserved "wiring" mechanism that can enable perturbations at specific surface positions to rapidly initiate conformational control over protein function. These findings suggest that sectors enable the evolution of intermolecular communication and regulation.

Original languageEnglish (US)
Pages (from-to)1564-1575
Number of pages12
JournalCell
Volume147
Issue number7
DOIs
StatePublished - Dec 23 2011

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Allosteric Regulation
Membrane Proteins
Basic Amino Acids
Tetrahydrofolate Dehydrogenase
Enzymes
Catalysis
Catalytic Domain
Proteins
Electric wiring
Communication

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Hot spots for allosteric regulation on protein surfaces. / Reynolds, Kimberly A.; McLaughlin, Richard N.; Ranganathan, Rama.

In: Cell, Vol. 147, No. 7, 23.12.2011, p. 1564-1575.

Research output: Contribution to journalArticle

Reynolds, KA, McLaughlin, RN & Ranganathan, R 2011, 'Hot spots for allosteric regulation on protein surfaces', Cell, vol. 147, no. 7, pp. 1564-1575. https://doi.org/10.1016/j.cell.2011.10.049
Reynolds, Kimberly A. ; McLaughlin, Richard N. ; Ranganathan, Rama. / Hot spots for allosteric regulation on protein surfaces. In: Cell. 2011 ; Vol. 147, No. 7. pp. 1564-1575.
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