Dartmouth Symposium for the Life Sciences: The Biology and Structure of Yeast Prions

Reed Wickner, chief researcher at the Laboratory of Biochemistry and Genetics at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), discussed the biology and structure of yeast prions at the Dartmouth Symposium for the Life Sciences this past Thursday.

Yeast prions are proteins that have the ability to self-propagate and cause normal proteins to undergo structural changes. These include [URE3], [PSI+], and [PIN+], all of which alters some aspect of the yeast phenotype. [URE3] enables yeast to grow in nitrogen-deficient environments; [PSI+] increases levels of nonsense genetic suppression; and [PIN+] induces other prions to accumulate.

Wickner explained that a protein could become any of several prion variants, each with distinct biological and physical properties. Furthermore, prion variants have different amyloid, or aggregate, forms, including the antiparallel beta-sheet, in-register parallel beta-sheet, and out-of-register parallel beta-sheet.

Wickner claimed that yeast prion amyloids have a “folded parellel in-register β-sheet structure,” meaning these amyloids consist of laterally connected strands that are oriented such that identical side chains are in line. Researchers arrived at this conclusion by using a variety of techniques, which included the measuring of the distance between strands in the beta-sheet and mass per length of filaments.

This architecture explains how a protein can template its own conformation. Hydrogen bonding and other interactions between the identical side chains keep yeast prion amyloids in-register (causing alignment). As a result, new monomers are incorporated into filaments to fit the inherent structural template.

At the close of the presentation, Wickner addressed the question: “Are yeast prions a help or hindrance?” He argued that most evidence suggests that these species are generally pathological. For one, [URE3] and [PSI+] are rare in wild yeast strains, which may indicate that they are more harmful than beneficial. Wickner went a step further and asserted that [URE3] and [PSI+] can be considered diseases of yeast cells. Additionally, he stated that cells exhibit stress reactions, namely heat shock protein induction, upon encountering prions.

Future research is required to understand the biology and structure of yeast prions, which will consequently provide insight into mammalian prions and their associated diseases.

Bookmark the permalink.

Leave a Reply

Your email address will not be published. Required fields are marked *