Dataset Information

Evolution of allostery in the cyclic nucleotide binding module.

ABSTRACT: The cyclic nucleotide binding (CNB) domain regulates signaling pathways in both eukaryotes and prokaryotes. In this study, we analyze the evolutionary information embedded in genomic sequences to explore the diversity of signaling through the CNB domain and also how the CNB domain elicits a cellular response upon binding to cAMP.Identification and classification of CNB domains in Global Ocean Sampling and other protein sequences reveals that they typically are fused to a wide variety of functional domains. CNB domains have undergone major sequence variation during evolution. In particular, the sequence motif that anchors the cAMP phosphate (termed the PBC motif) is strikingly different in some families. This variation may contribute to ligand specificity inasmuch as members of the prokaryotic cooA family, for example, harbor a CNB domain that contains a non-canonical PBC motif and that binds a heme ligand in the cAMP binding pocket. Statistical comparison of the functional constraints imposed on the canonical and non-canonical PBC containing sequences reveals that a key arginine, which coordinates with the cAMP phosphate, has co-evolved with a glycine in a distal beta2-beta3 loop that allosterically couples cAMP binding to distal regulatory sites.Our analysis suggests that CNB domains have evolved as a scaffold to sense a wide variety of second messenger signals. Based on sequence, structural and biochemical data, we propose a mechanism for allosteric regulation by CNB domains.

SUBMITTER: Kannan N

PROVIDER: S-EPMC2246266 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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Evolution of allostery in the cyclic nucleotide binding module.

Kannan Natarajan N Wu Jian J Anand Ganesh S GS Yooseph Shibu S Neuwald Andrew F AF Venter J Craig JC Taylor Susan S SS

Genome biology 20070101 12

<h4>Background</h4>The cyclic nucleotide binding (CNB) domain regulates signaling pathways in both eukaryotes and prokaryotes. In this study, we analyze the evolutionary information embedded in genomic sequences to explore the diversity of signaling through the CNB domain and also how the CNB domain elicits a cellular response upon binding to cAMP.<h4>Results</h4>Identification and classification of CNB domains in Global Ocean Sampling and other protein sequences reveals that they typically are ...[more]

PMID: 18076763

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Project description:BackgroundThere is increasing demand to test hypotheses that contrast the evolution of genes and gene families among genomes, using simulations that work across these levels of organization. The EvolSimulator program was developed recently to provide a highly flexible platform for forward simulations of amino acid evolution in multiple related lineages of haploid genomes, permitting copy number variation and lateral gene transfer. Synonymous nucleotide evolution is not currently supported, however, and would be highly advantageous for comparisons to full genome, transcriptome, and single nucleotide polymorphism (SNP) datasets. In addition, EvolSimulator creates new genomes for each simulation, and does not allow the input of user-specified sequences and gene family information, limiting the incorporation of further biological realism and/or user manipulations of the data.FindingsWe present modified C++ source code for the EvolSimulator platform, which we provide as the extension module NU-IN. With NU-IN, synonymous and non-synonymous nucleotide evolution is fully implemented, and the user has the ability to use real or previously-simulated sequence data to initiate a simulation of one or more lineages. Gene family membership can be optionally specified, as well as gene retention probabilities that model biased gene retention. We provide PERL scripts to assist the user in deriving this information from previous simulations. We demonstrate the features of NU-IN by simulating genome duplication (polyploidy) in the presence of ongoing copy number variation in an evolving lineage. This example is initiated with real genomic data, and produces output that we analyse directly with existing bioinformatic pipelines.ConclusionsThe NU-IN extension module is a publicly available open source software (GNU GPLv3 license) extension to EvolSimulator. With the NU-IN module, users are now able to simulate both drift and selection at the nucleotide, amino acid, copy number, and gene family levels across sets of related genomes, for user-specified starting sequences and associated parameters. These features can be used to generate simulated genomic datasets under an extremely broad array of conditions, and with a high degree of biological realism.

Dataset Information

Evolution of allostery in the cyclic nucleotide binding module.

Publications

Evolution of allostery in the cyclic nucleotide binding module.

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