Allostery is one of most important processes in molecular biology by
which proteins transmit the information from one functional site to another,
frequently distant site. The information on ligand binding or on posttranslational
modification at one site is transmitted along allosteric communication path to
another functional site allowing for regulation of protein activity. The detailed
analysis of the general character of allosteric communication paths is therefore
extremely important. It enables to better understand the mechanism of allostery
and can be used in for the design of new generations of drugs.
Considering all the PDB annotated allosteric proteins (from ASD - AlloSteric
Database) belonging to four different classes (kinases, nuclear receptors, peptidases
and transcription factors), this work has attempted to decipher certain
consistent patterns present in the residues constituting the allosteric communication
sub-system (ACSS). The thermal fluctuations of hydrophobic residues in
ACSSs were found to be significantly higher than those present in the non-
ACSS part of the same proteins, while polar residues showed the opposite trend.
The basic residues and hydroxyl residues were found to be slightly more
predominant than the acidic residues and amide residues in ACSSs, hydrophobic
residues were found extremely frequently in kinase ACSSs. Despite having
different sequences and different lengths of ACSS, they were found to be
structurally quite similar to each other – suggesting a preferred structural template
for communication. ACSS structures recorded low RMSD and high
Akaike Information Criterion (AIC) scores among themselves. While the ACSS
networks for all the groups of allosteric proteins showed low degree centrality
and closeness centrality, the betweenness centrality magnitudes revealed
nonuniform behavior. Though cliques and communities could be identified
within the ACSS, maximal-common-subgraph considering all the ACSS could
not be generated, primarily due to the diversity in the dataset. Barring one
particular case, the entire ACSS for any class of allosteric proteins did not demonstrate “small world” behavior, though the sub-graphs of the ACSSs, in
certain cases, were found to form small-world networks.
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Cryo-EM structure of rhinovirus C15a bound to its cadherin-related protein 3 receptor
Infection by
- NSF-PAR ID:
- 10138827
- Publisher / Repository:
- Proceedings of the National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 117
- Issue:
- 12
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- p. 6784-6791
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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