Emily Byrd

🚨Happy to share our preprint 👇🏼

🔬We used submicron nanopipette emitters to probe the conformational ensemble of α-synuclein in biochemical buffer systems using native ion mobility mass spectrometry.🧩

Zn2+ Binding Shifts the Conformational Ensemble of α-Synuclein Monomers toward Accelerated Amyloid Formation Alpha-synuclein (αS) is an intrinsically disordered protein (IDP) that can self-assemble into amyloid fibrils, undergoing a transition from disordered monomers to ordered β-sheet-rich fibrils. The amy...

🚨 Excited to share our paper in JACS!
📈 We show that Zn²⁺ ions modulate the conformational ensemble of N-acetylated α-synuclein which directly influences its amyloidogenic behaviour.
🧩 Our approach combines ion mobility mass spec with ThT fluorescence, NMR and MD.
👉🏼 pubs.acs.org/doi/10.1021/...

Recovering from a fantastic week at #ASMS2025 🌎! I am so grateful to have had the opportunity to present at the Waters Corporation Users Meeting and the ASMS Structural Biology session 🧠.

It was a great chance to reconnect with old friends, make new connections, and receive valuable feedback 📈.

Had a great day at #UCLA 🐻 for @emilyjbyrd.bsky.social's seminar. Huge thanks to @joelooucla.bsky.social for hosting us and giving us a campus tour!

Hydrogen–Deuterium Exchange Mass Spectrometry Reveals Mechanistic Insights into RNA Oligonucleotide-Mediated Inhibition of TDP-43 Aggregation Deposits of aggregated TAR DNA-binding protein 43 (TDP-43) in the brain are associated with several neurodegenerative diseases. It is well established that binding of RNA/DNA to TDP-43 can prevent TDP-43 aggregation, but an understanding of the structure(s) and conformational dynamics of TDP-43, and TDP-43-RNA complexes, is lacking, including knowledge of how the solution environment modulates these properties. Here, we address this challenge using hydrogen–deuterium exchange-mass spectrometry. In the presence of RNA olignoucleotides, we observe protection from exchange in the RNA recognition motif (RRM) domains of TDP-43 and the linker region between the RRM domains, consistent with nucleic acid binding modulating interdomain interactions. Intriguingly, at elevated salt concentrations, the extent of protection from exchange is reduced in the RRM domains when bound to an RNA sequence derived from the 3′ UTR of the TDP-43 mRNA (CLIP34NT) compared to when bound to a (UG)6 repeat sequence. Under these conditions, CLIP34NT is no longer able to prevent TDP-43 aggregation. This suggests that a salt-induced structural rearrangement occurs when bound to this RNA, which may play a role in facilitating aggregation. Additionally, upon RNA binding, we identify differences in exchange within the short α-helical region located in the C-terminal domain (CTD) of TDP-43. These allosterically altered regions may influence the ability of TDP-43 to aggregate and fine-tune its RNA binding repertoire. Combined, these data provide additional insights into the intricate interplay between TDP-43 aggregation and RNA binding, an understanding of which is crucial for unraveling the molecular mechanisms underlying TDP-43-associated neurodegeneration.

Hydrogen–Deuterium Exchange Mass Spectrometry Reveals Mechanistic Insights into RNA Oligonucleotide-Mediated Inhibition of TDP-43 Aggregation #JACS pubs.acs.org/doi/10.1021/...