To investigate protein evolution by detecting suppressed epitope structures.
Material remains of ancestor nucleotides and proteins are largely unavailable, thus sequence comparison among homologous genes in present-day organisms forms the core of current knowledge of molecular evolution. Variation in protein three-dimensional structure is a basis for functional diversity. To study the evolution of three-dimensional structures in related proteins would significantly improve our understanding of protein evolution and function. A protein may contain ancestor conformations that have been allosterically suppressed by evolutionarily additive structures. Using monoclonal antibody probes to detect such conformation in proteins after removing the suppressor structure, our study demonstrates three-dimensional structure evidence for the evolutionary relationship between troponin I and troponin T, two subunits of the troponin complex in the Ca(2+)-regulatory system of striated muscle, and among their muscle type-specific isoforms. The experimental data show the feasibility of detecting evolutionarily suppressed history-telling structural states in proteins by removing conformational modulator segments added during evolution. In addition to identifying structural modifications that were critical to the emergence of diverged proteins, investigating this novel mode of evolution will help us to understand the origin and functional potential of protein structures.
Section of Molecular Cardiology, Evanston Northwestern Healthcare and Northwestern University, 2650 Ridge Avenue, Evanston, IL 60201, USA.
Stephen M
SM
Chong
J-P
JP
Jin
D000818:Animals; D000911:Antibodies, Monoclonal; D003429:Cross Reactions; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry*; D019143:Evolution, Molecular; D006801:Humans; D008954:Models, Biological; D010802:Phylogeny; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000737:chemistry* / Q000276:immunology; D020539:Sequence Analysis, Protein; D019210:Troponin I / Q000235:genetics; D020107:Troponin T / Q000235:genetics
D000911:Antibodies, Monoclonal; D000939:Epitopes; D020033:Protein Isoforms; D011506:Proteins; D019210:Troponin I; D020107:Troponin T