Functional Divergence in Teleost Cardiac Troponin Paralogs Guides Variation in the Interaction of TnI Switch Region with TnC
| Autor: | Charles M. Stevens, Christine E. Genge, D. Peter Tieleman, Glen F. Tibbits, Gurpreet Singh, William S. Davidson |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular Multiprotein complex Acclimatization molecular coevolution Biology Troponin C Evolution Molecular 03 medical and health sciences Gene duplication functional divergence Genetics Animals Amino Acid Sequence Protein Interaction Maps protein interaction Selection Genetic Gene Zebrafish Ecology Evolution Behavior and Systematics Phylogeny structural subfunctionalization 030102 biochemistry & molecular biology troponin Gene Expression Profiling Troponin I regulatory subfunctionalization biology.organism_classification musculoskeletal system Cold Temperature 030104 developmental biology Evolutionary biology cardiovascular system Subfunctionalization Functional divergence Function (biology) Research Article |
| Zdroj: | Genome Biology and Evolution |
| ISSN: | 1759-6653 |
| Popis: | Gene duplication results in extra copies of genes that must coevolve with their interacting partners in multimeric protein complexes. The cardiac troponin (Tn) complex, containing TnC, TnI, and TnT, forms a distinct functional unit critical for the regulation of cardiac muscle contraction. In teleost fish, the function of the Tn complex is modified by the consequences of differential expression of paralogs in response to environmental thermal challenges. In this article, we focus on the interaction between TnI and TnC, coded for by genes that have independent evolutionary origins, but the co-operation of their protein products has necessitated coevolution. In this study, we characterize functional divergence of TnC and TnI paralogs, specifically the interrelated roles of regulatory subfunctionalization and structural subfunctionalization. We determined that differential paralog transcript expression in response to temperature acclimation results in three combinations of TnC and TnI in the zebrafish heart: TnC1a/TnI1.1, TnC1b/TnI1.1, and TnC1a/TnI1.5. Phylogenetic analysis of these highly conserved proteins identified functionally divergent residues in TnI and TnC. The structural and functional effect of these Tn combinations was modeled with molecular dynamics simulation to link divergent sites to changes in interaction strength. Functional divergence in TnI and TnC were not limited to the residues involved with TnC/TnI switch interaction, which emphasizes the complex nature of Tn function. Patterns in domain-specific divergent selection and interaction energies suggest that substitutions in the TnI switch region are crucial to modifying TnI/TnC function to maintain cardiac contraction with temperature changes. This integrative approach introduces Tn as a model of functional divergence that guides the coevolution of interacting proteins. |
| Databáze: | OpenAIRE |
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