Elucidating functional roles of dynamics in sequential biosynthesis and protein oligomerization
Proteins perform biological functions critical to all aspects of life. Influenced by perpetual thermal fluctuations, protein dynamics span a wide range of temporal and spatial scales. Yet, a quantitative, mechanistic, and ultimately predictive understanding on how protein dynamics and functions are coupled remains elusive. In my presentation, I will describe my research using single-molecule Förster resonance energy transfer (smFRET) and solution nuclear magnetic resonance (NMR) spectroscopy respectively to elucidate key roles of protein dynamics in driving biosynthesis of an antibiotic peptide and reversible assembly of an amyloidogenic protein.
In the first part of my talk, I will describe the discovery of a novel conformation that is more structurally extended than known X-ray structures for a non-ribosomal peptide synthetase using time-dependent smFRET. We quantitatively integrate smFRET with small-angle X-ray scattering and molecular dynamics simulations to reveal that the extended conformation is needed to coordinate sequential chemical transformations where the biosynthetic directionality is driven by the enzyme's innate conformational free energies.
In the second part, I will present how we probe dissociation and aggregation pathways of human transthyretin by combining solution NMR and computational modeling. We develop an integrative platform to unravel quantitative details regarding a dimer-mediated dissociation and reassembly process of transthyretin and probe a minor conformation that is more prone to aggregation than the native tetrameric conformation.
Hosted by Professor Andy Nieuwkoop
~Coffee/tea will be served prior to the lecture~