Abstract:
An amyloid protein belongs to a group of intrinsically disordered proteins (IDPs). Self-assembly of IDPs imparts toxic biological effects depending on the size in over 20 neurodegenerative diseases. Unfortunately, our understanding of amyloid polypeptides, as related to biomedical implications, is limited by their self-assembling nature. On the other hand, due to high structural flexibility, occasionally coupled with functional roles, Nature often uses IDPs as structure-switching biosensors for rapid and specific signaling processes. Thus, IDPs may serve as a new source of proteins that can readily be engineered into molecular sensors with unique sensing behaviors. In this talk, I will first present our study on the creation of a dual peptide system, where a pair of engineered b-amyloid (Ab) variants, KLVFWAK and ELVFWAE, are not self-assembled but hetero-assembled in the presence of their assembly partners. We provide evidence that the resulting hetero-assemblies share molecular, structural and morphological similarities with typical amyloid self-assemblies formed by a single polypeptide (e.g., Ab). We anticipate that our dual peptide system may readily be adapted for precise control of amyloid assembly, for the study of size-dependent neurotoxicity. I will also describe our engineering efforts to create structurally flexible amyloid protein variants. These engineered proteins rapidly generate distinct fluorescence responses to the three major amyloid conformers (monomers, oligomers, and fibrils), as molecular sensors to profile aggregation states critical for neuropathology.
Unlike IDPs, globular proteins fold into compact structures, responsible for various biological functions. Interestingly, globular proteins also form amyloid fibrils under partially denaturing conditions, demonstrating that amyloid aggregation is a generic property of proteins. In the second half of my talk, I will present our recent study, where a globular protein, Bacillus circulans xylanase (BCX), aggregates into amyloid fibrils under native conditions. Interestingly, addition of KLVFWAK or ELVFWAE modulated the BCX amyloid aggregation. This study also provides insight into a correlation between kinetic stability and amyloid aggregation of BCX, and supports a view that IDP-derived peptide fragments can modulate amyloid aggregation of globular proteins. Lastly, I will discuss industrial implications of amyloid aggregation by globular proteins under non-denaturing conditions.
Overall, my talk will present new engineering opportunities with IDPs and illustrate overlooked molecular features shared between IDPs and globular proteins.
Biography:
Jin Ryoun Kim is an associate professor in the Department of Chemical and Biomolecular Engineering at New York University (NYU). Prior to his career at NYU, he earned his BS and MS degrees at Seoul National University and his PhD degree at the University of Wisconsin-Madison majoring in chemical engineering, followed by his postdoctoral research at Johns Hopkins University. He is interested in protein design to solve problems related to protein stability, misfolding, aggregation and self-assembly. His research has been supported by NSF, NIH, the Alzheimer’s association, the Ines Mandl Research Foundation and other funding agencies.
Thursday, December 1, 2022
9:30 a.m., Gant North (GN) 20
Livestream URL: http://www.kaltura.com/tiny/lqwur
Refreshments will be served at 9:15 a.m.
For more information, contact: Katie O'Keefe/Chemical & Biomolecular Engineering Department at 860-486-6096/katie.okeefe@uconn.edu