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Full-Text Articles in Physics
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 …
Determining The Molecular Mechanisms Of Huntington’S Disease Through Multi-Scale Modeling, Kiersten Ruff
Determining The Molecular Mechanisms Of Huntington’S Disease Through Multi-Scale Modeling, Kiersten Ruff
Arts & Sciences Electronic Theses and Dissertations
Huntington’s disease (HD) is associated with a mutational CAG repeat expansion within exon 1 of the huntingtin (Htt) gene. Post-transcriptional processing leads to the generation of N-terminal Htt protein fragments (Htt-NTFs), including those that encompass exon 1 (Httex1). Within Httex1, the CAG-repeat encoded polyglutamine (polyQ) tract is flanked N-terminally by a 17-residue amphipathic stretch (N17) and C-terminally by a 50-residue proline rich (PR) domain. Htt-NTFs, including Httex1, are among the smallest fragments that recapitulate HD pathology in mouse models. However, the direct link between Htt-NTFs with polyQ expansions and neurodegeneration that leads to HD remains unresolved. Despite being a monogenic …