A Fifth of the Protein World: Rossmann-like Proteins as an Evolutionarily Successful Structural unit |
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| Institution: | 1. Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, United States;2. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, United States;3. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, United States;1. University of Colorado Anschutz Medical Campus, Department of Biochemistry and Molecular Genetics, 12801 East 17th Avenue, Aurora, Colorado 80045, USA;2. Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;3. Anderson University, Department of Chemistry and Biology, 316 Boulevard, Anderson, SC 29621, USA;1. Goodman Cancer Research Centre, McGill University, 1160 Pine Avenue West, Montreal, Québec H3A 1A3, Canada;2. Departments of Biochemistry, McGill University, 1160 Pine Avenue West, Montreal, Québec H3A 1A3, Canada;3. Medicine, McGill University, 1160 Pine Avenue West, Montreal, Québec H3A 1A3, Canada;4. Oncology, McGill University, 1160 Pine Avenue West, Montreal, Québec H3A 1A3, Canada;5. Department of Biology, Faculté des sciences, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada;6. Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, Sherbrooke, Québec J1K 2R1, Canada;1. Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, United States;2. Department of Chemistry, Dartmouth College, Hanover, NH 03755, United States;3. Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, United States |
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| Abstract: | The Rossmann-like fold is the most prevalent and diversified doubly-wound superfold of ancient evolutionary origin. Rossmann-like domains are present in a variety of metabolic enzymes and are capable of binding diverse ligands. Discerning evolutionary relationships among these domains is challenging because of their diverse functions and ancient origin. We defined a minimal Rossmann-like structural motif (RLM), identified RLM-containing domains among known 3D structures (20%) and classified them according to their homologous relationships. New classifications were incorporated into our Evolutionary Classification of protein Domains (ECOD) database. We defined 156 homology groups (H-groups), which were further clustered into 123 possible homology groups (X-groups). Our analysis revealed that RLM-containing proteins constitute approximately 15% of the human proteome. We found that disease-causing mutations are more frequent within RLM domains than within non-RLM domains of these proteins, highlighting the importance of RLM-containing proteins for human health. |
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| Keywords: | Rossmann-fold minimal Rossmann-like motif protein evolution domains classification |
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