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Substrate selection in endoplasmic reticulum protein quality control

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dc.contributor.advisorDaniel N Hebert
dc.contributor.authorAdams, Ben
dc.contributor.departmentUniversity of Massachusetts Amherst
dc.date2024-03-27T17:32:03.000
dc.date.accessioned2024-04-26T15:43:03Z
dc.date.available2024-04-26T15:43:03Z
dc.date.submittedFebruary
dc.date.submitted2021
dc.description.abstractProtein folding and maturation is a complex and error-prone process. Errors in this process may lead to deleterious effects ranging from non-functional single proteins to large-scale protein aggregation leading to cell death. It is essential for cellular function that protein misfolding does not occur unchecked, and therefore numerous chaperone systems exist within the cell. For the thousands of proteins which traffic through the secretory pathway, the primary site of folding and maturation is the endoplasmic reticulum (ER). Multiple chaperone pathways within the ER, generally termed ER protein quality control, must support the proper maturation process of these thousands of substrates. While some simple secretory pathway proteins may be able to fold with minimal chaperone engagement, more complex proteins may commonly misfold even under native conditions, which is especially important for multi-cellular organisms which have larger and more complex secretory pathway proteomes. The chaperone pathways within the ER engage substrates based generally on features those substrates possess. These include hydrophobic regions, free cysteines, and N-glycans. However, which substrates are selected by each of these pathways is not well understood on a systematic level. The work presented here examines the chaperone selection process for a substrate which possess all features and demonstrates that substrate features do not dictate chaperone pathway engagement. As such, an understanding of which substrates are engaged by which pathway under endogenous conditions requires experimental determination. The N-glycan based chaperone pathway was next examined, and the substrates which heavily engage this process under endogenous conditions were described. This information allows for a previously lacking understanding of the folding and maturation process of many proteins and therefore presents possible interventions for the diseases and cellular functions associated with these proteins.
dc.description.degreeDoctor of Philosophy (PhD)
dc.description.departmentMolecular and Cellular Biology
dc.identifier.doihttps://doi.org/10.7275/20681399
dc.identifier.orcidhttps://orcid.org/0000-0002-9980-5321
dc.identifier.urihttps://hdl.handle.net/20.500.14394/18378
dc.relation.urlhttps://scholarworks.umass.edu/cgi/viewcontent.cgi?article=3205&context=dissertations_2&unstamped=1
dc.source.statuspublished
dc.subjectEndoplasmic Reticulum
dc.subjectprotein quality control
dc.subjectchaperones
dc.subjectUGGT1
dc.subjectUGGT2
dc.subjectCell Biology
dc.titleSubstrate selection in endoplasmic reticulum protein quality control
dc.typeopenaccess
dc.typearticle
dc.typedissertation
digcom.contributor.authorisAuthorOfPublication|email:benjamin.adams34@gmail.com|institution:University of Massachusetts Amherst|Adams, Ben
digcom.identifierdissertations_2/2088
digcom.identifier.contextkey20681399
digcom.identifier.submissionpathdissertations_2/2088
dspace.entity.typePublication
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