Biochemistry Commons^™

Elucidating The Proteasomal Regulatory Mechanism Of Proteasome Activator Pa28Γ /Regγ, Taylor Ann Thomas

Graduate Theses, Dissertations, and Problem Reports

Virtually all cellular processes are precisely regulated by the proteasome which is the primary enzyme responsible for the degradation of misfolded, damaged, or no longer necessary soluble proteins. To prevent any untimely degradation of these target protein substrates and protect the cell, the proteasome is tightly regulated via adaptor proteins, known as proteasomal regulators. There are many classes of proteasomal regulators each with their own unique structures, functions, and effects on protein degradation through the proteasome. One such class is the 11S family of proteasomal regulators which are also referred to as PA26/28, or REG. The 11S family are ATP-independent …

Huntingtin Aggregation At Interfaces Associated With Membranes And Organelles, Adewale Vincent Adegbuyiro

Graduate Theses, Dissertations, and Problem Reports

Huntington’s Disease (HD) is a genetic neurodegenerative disease caused by the expansion of polyglutamine (polyQ) domain within the first exon (exon1) of the huntingtin (htt) protein. Due to this mutation within the polyQ domain, htt aggregates into various toxic species such as oligomers, fibrils, and other amorphous aggregates. While the aggregation of htt strongly correlates with polyQ length, other factors, e.g. interaction with membranes or organelles and posttranslational modifications (PTMs), modulate aggregation. The first 17 N-terminal amino acids (Nt17) that precede the polyQ in htt-exon1 enhances aggregation and facilitated binding of htt to membranous organelles, promoting morphological changes and disfunction. …

Understanding The Relationship Between Local Environmental Changes And The Function Of The Ph Low Insertion Peptide, Violetta Burns Casamayor

Graduate Theses, Dissertations, and Problem Reports

Cancer is the second leading cause of death in the US with over 1.7 million new cases each year. Current cancer treatments tend to also target healthy tissues due to similarities with cancerous ones, resulting in acute side effects. Early detection is the best approach towards defeating cancer, however, modern imaging techniques require sizeable samples, often implying a late stage in the disease. One common attribute of tumors is their acidic microenvironment, which can be taken advantage of.

The pH Low Insertion Peptide (pHLIP) is a membrane-active peptide that can take advantage of the acidic microenvironment surrounding cancer cells. pHLIP …

The Effects Of Membrane Physicochemical Properties On Huntingtin Membrane Association And Downstream Aggregation, Maryssa Beasley

Graduate Theses, Dissertations, and Problem Reports

Huntington’s Disease (HD) is a fatal neurodegenerative disorder caused by an expanded glutamine repeat region (polyQ) within the huntingtin protein (htt). As a result of the expanded polyQ domain, htt associates into a variety of toxic aggregate species. The polyQ domain of htt is flanked at the N-terminal end by 17 amino acids (Nt17) that adopt an amphipathic α-helical structure in the presence of binding partners such as lipid membranes. In addition to comprising a lipid binding domain, the Nt17 amphipathic α -helix has been directly implicated in htt aggregation initiation via self-association with other Nt17 α -helices. Due to …