Evolutionarily conserved networks of residues mediate allosteric communication in proteins

@article{Sel2003EvolutionarilyCN,
  title={Evolutionarily conserved networks of residues mediate allosteric communication in proteins},
  author={G{\"u}rol M. S{\"u}el and S. W. Lockless and M. Wall and R. Ranganathan},
  journal={Nature Structural Biology},
  year={2003},
  volume={10},
  pages={59-69}
}
A fundamental goal in cellular signaling is to understand allosteric communication, the process by which signals originating at one site in a protein propagate reliably to affect distant functional sites. The general principles of protein structure that underlie this process remain unknown. Here, we describe a sequence-based statistical method for quantitatively mapping the global network of amino acid interactions in a protein. Application of this method for three structurally and functionally… Expand

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References

SHOWING 1-10 OF 66 REFERENCES
Evolutionarily conserved pathways of energetic connectivity in protein families.
TLDR
Mutational studies confirm that the statistical energy function is a good indicator of thermodynamic coupling in proteins, demonstrating that sets of interacting residues form connected pathways through the protein fold that may be the basis for efficient energy conduction within proteins. Expand
The linkage between protein folding and functional cooperativity: two sides of the same coin?
TLDR
The statistical thermodynamic linkage between protein stability, functional cooperativity, and ligand binding is discussed and the distribution of stabilizing interactions does not only provide the architectural foundation to the three-dimensional structure of a protein, but it also provides the required framework forfunctional cooperativity. Expand
Crystal structure of rhodopsin: a G-protein-coupled receptor.
Heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) respond to a variety of different external stimuli and activate G proteins. GPCRs share many structuralExpand
An evolutionary trace method defines binding surfaces common to protein families.
TLDR
The evolutionary trace method is a systematic, transparent and novel predictive technique that identifies active sites and functional interfaces in proteins with known structure and provides an evolutionary perspective for judging the functional or structural role of each residue in protein structure. Expand
Uncovering molecular mechanisms involved in activation of G protein-coupled receptors.
  • U. Gether
  • Biology, Medicine
  • Endocrine reviews
  • 2000
TLDR
The goal of the present review is to specifically address the physical changes linking agonist binding to receptor activation and subsequent transduction of the signal to the associated G protein on the cytoplasmic side of the membrane and to other putative signaling pathways. Expand
How frequent are correlated changes in families of protein sequences?
  • E. Neher
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1994
TLDR
A statistical theory is presented which allows evaluation of correlations in a family of aligned protein sequences by assigning a scalar metric to each type of amino acid and calculating correlation coefficients of these quantities at different positions and it is found that there is a high correlation between fluctuations in neighboring charges. Expand
Backbone dynamics in dihydrofolate reductase complexes: role of loop flexibility in the catalytic mechanism.
TLDR
The relaxation data for Escherichia coli dihydrofolate reductase are measured to provide insights into the changes in backbone dynamics during the catalytic cycle and point to an important role of the Met20 and betaF-betaG loops in controlling access to the active site. Expand
Structural mimicry in G protein-coupled receptors: implications of the high-resolution structure of rhodopsin for structure-function analysis of rhodopsin-like receptors.
TLDR
It is proposed that the overall structures of rhodopsin and of amine receptors are very similar, although there are also localized regions where the structure of these receptors may diverge. Expand
Regulation of the rhodopsin-transducin interaction by a highly conserved carboxylic acid group.
TLDR
The data suggest that the protonated state of Glu-134 favors binding of rhodopsin to transducin and that Glu/Asp/Arg/Tyr is not titratable in the rhodopin-transducin complex. Expand
Detecting protein function and protein-protein interactions from genome sequences.
TLDR
Searching sequences from many genomes revealed 6809 putative protein-protein interactions in Escherichia coli and 45,502 in yeast, and many members of these pairs were confirmed as functionally related; computational filtering further enriches for interactions. Expand
...
1
2
3
4
5
...