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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Sequence Determinants Of The Individual And Collective Behaviour Of Intrinsically Disordered Proteins, Alexander S. Holehouse
Sequence Determinants Of The Individual And Collective Behaviour Of Intrinsically Disordered Proteins, Alexander S. Holehouse
Arts & Sciences Electronic Theses and Dissertations
Intrinsically disordered proteins and protein regions (IDPs) represent around thirty percent of the eukaryotic proteome. IDPs do not fold into a set three dimensional structure, but instead exist in an ensemble of inter-converting states. Despite being disordered, IDPs are decidedly not random; well-defined - albeit transient - local and long-range interactions give rise to an ensemble with distinct statistical biases over many length-scales. Among a variety of cellular roles, IDPs drive and modulate the formation of phase separated intracellular condensates, non-stoichiometric assemblies of protein and nucleic acid that serve many functions. In this work, we have explored how the amino …
Disordered Proteins: Connecting Sequences To Emergent Properties, Tyler Scott Harmon
Disordered Proteins: Connecting Sequences To Emergent Properties, Tyler Scott Harmon
Arts & Sciences Electronic Theses and Dissertations
Many IDPs participate in coupled folding and binding reactions and form alpha helical structures in their bound complexes. Alanine, glycine, or proline scanning mutagenesis approaches are often used to dissect the contributions of intrinsic helicities to coupled folding and binding. These experiments can yield confounding results because the mutagenesis strategy changes the amino acid compositions of IDPs. Therefore, an important next step in mutagenesis-based approaches to mechanistic studies of coupled folding and binding is the design of sequences that satisfy three major constraints. These are (i) achieving a target intrinsic alpha helicity profile; (ii) fixing the positions of residues corresponding …