title: From A to B: a ride in the free energy surfaces of protein G domains suggests how new folds arise.
abstract: Metamorphic proteins are an extremely intriguing case of protein evolution and a golden opportunity to challenge the current simplified models. In a recent work, we showed that a coarse-grained Gō model can be used to study the thermodynamics of lymphotactin, a naturally occurring metamorphic protein. Here, we extend such model by including the necessary atomic detail to study the effects of the single mutations that artificially bring the GA domain of protein G to fold into the GB domain of the same protein. The results of this all-atom Gō model show how the residual structure of the denatured state is an early indicator of a forthcoming fold and function switch. These findings reconcile the results of previous studies on similar systems highlighting the different role played by secondary and tertiary interactions and suggesting a possible way for new folds to arise.
authors.affiliation: Spanish National Cancer Research Center (CNIO), Structural Biology and Biocomputing Programme, Melchor Fernandez Almagro 3, E-28029 Madrid, Spain. lsutto@cnio.es
authors.forename: Ludovico
authors.initials: L
authors.lastname: Sutto
authors.forename: Carlo
authors.initials: C
authors.lastname: Camilloni
mesh_terms: D000595:Amino Acid Sequence; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013696:Temperature; D013816:Thermodynamics
chemical_list: D019206:GTP-Binding Protein alpha Subunits, Gi-Go