Stability Effect of Quinary Interactions Reversed by Single Point Mutations. 2019

David Gnutt, and Stepan Timr, and Jonas Ahlers, and Benedikt König, and Emily Manderfeld, and Matthias Heyden, and Fabio Sterpone, and Simon Ebbinghaus
Institute of Physical and Theoretical Chemistry , TU Braunschweig , Rebenring 56 , Braunschweig 38106 , Germany.

In cells, proteins are embedded in a crowded environment that controls their properties via manifold avenues including weak protein-macromolecule interactions. A molecular level understanding of these quinary interactions and their contribution to protein stability, function, and localization in the cell is central to modern structural biology. Using a mutational analysis to quantify the energetic contributions of single amino acids to the stability of the ALS related protein superoxide dismutase I (SOD1) in mammalian cells, we show that quinary interactions destabilize SOD1 by a similar energetic offset for most of the mutants, but there are notable exceptions: Mutants that alter its surface properties can even lead to a stabilization of the protein in the cell as compared to the test tube. In conclusion, quinary interactions can amplify and even reverse the mutational response of proteins, being a key aspect in pathogenic protein misfolding and aggregation.

UI MeSH Term Description Entries
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D004795 Enzyme Stability The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat. Enzyme Stabilities,Stabilities, Enzyme,Stability, Enzyme
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072105 Superoxide Dismutase-1 A superoxide dismutase (SOD1) that requires copper and zinc ions for its activity to destroy SUPEROXIDE FREE RADICALS within the CYTOPLASM. Mutations in the SOD1 gene are associated with AMYOTROPHIC LATERAL SCLEROSIS-1. Cu-Zn Superoxide Dismutase,Cuprozinc Superoxide Dismutase,SOD-1 Protein,SOD1 Protein,Superoxide Dismutase 1,Cu Zn Superoxide Dismutase,SOD 1 Protein,Superoxide Dismutase, Cu-Zn,Superoxide Dismutase, Cuprozinc
D017354 Point Mutation A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. Mutation, Point,Mutations, Point,Point Mutations
D056004 Molecular Dynamics Simulation A computer simulation developed to study the motion of molecules over a period of time. Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics

Related Publications

David Gnutt, and Stepan Timr, and Jonas Ahlers, and Benedikt König, and Emily Manderfeld, and Matthias Heyden, and Fabio Sterpone, and Simon Ebbinghaus
December 1990, The Journal of biological chemistry,
David Gnutt, and Stepan Timr, and Jonas Ahlers, and Benedikt König, and Emily Manderfeld, and Matthias Heyden, and Fabio Sterpone, and Simon Ebbinghaus
March 2019, The journal of physical chemistry. B,
David Gnutt, and Stepan Timr, and Jonas Ahlers, and Benedikt König, and Emily Manderfeld, and Matthias Heyden, and Fabio Sterpone, and Simon Ebbinghaus
February 1991, Biotechnology and applied biochemistry,
David Gnutt, and Stepan Timr, and Jonas Ahlers, and Benedikt König, and Emily Manderfeld, and Matthias Heyden, and Fabio Sterpone, and Simon Ebbinghaus
November 2012, Protein engineering, design & selection : PEDS,
David Gnutt, and Stepan Timr, and Jonas Ahlers, and Benedikt König, and Emily Manderfeld, and Matthias Heyden, and Fabio Sterpone, and Simon Ebbinghaus
November 2004, Angewandte Chemie (International ed. in English),
David Gnutt, and Stepan Timr, and Jonas Ahlers, and Benedikt König, and Emily Manderfeld, and Matthias Heyden, and Fabio Sterpone, and Simon Ebbinghaus
December 2019, Biomolecules,
David Gnutt, and Stepan Timr, and Jonas Ahlers, and Benedikt König, and Emily Manderfeld, and Matthias Heyden, and Fabio Sterpone, and Simon Ebbinghaus
March 2008, BMC bioinformatics,
David Gnutt, and Stepan Timr, and Jonas Ahlers, and Benedikt König, and Emily Manderfeld, and Matthias Heyden, and Fabio Sterpone, and Simon Ebbinghaus
January 2021, International journal of molecular sciences,
David Gnutt, and Stepan Timr, and Jonas Ahlers, and Benedikt König, and Emily Manderfeld, and Matthias Heyden, and Fabio Sterpone, and Simon Ebbinghaus
February 2015, Proceedings of the National Academy of Sciences of the United States of America,
David Gnutt, and Stepan Timr, and Jonas Ahlers, and Benedikt König, and Emily Manderfeld, and Matthias Heyden, and Fabio Sterpone, and Simon Ebbinghaus
December 2007, Biochemical Society transactions,
Copied contents to your clipboard!