| Autor: |
George L. Hamilton, Inna S. Yanez-Orozco, Erkang Ou, Tatyana I. Smirnova, Nabanita Saikia, Sergey Milikisiyants, Ruoyi Qiu, Keith Weninger, Feng Ding, Hugo Sanabria, Pengyu Hao |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| DOI: |
10.2139/ssrn.3844745 |
| Popis: |
SNAP-25 (synaptosomal-associated protein of 25 kDa) is a prototypical intrinsically disordered protein (IDP) that is unstructured in its unbound form but forms coiled-coil helices in the SNARE complex. With high conformational heterogeneity, detailed structural dynamics of unbound SNAP-25 remains elusive. Here, we present an integrative method to probe the structural dynamics of SNAP-25 by combining replica-exchange discrete molecular dynamics (rxDMD) simulations and label-based experiments at ensemble and single-molecule levels. The rxDMD simulation allows us to systematically characterize the coil-to-molten-globular transition and reconstruct structural ensemble consistent with prior ensemble experiments. Label-based experiments using Forster Resonance Energy Transfer and Double Electron Electron Resonance further probe the conformational dynamics of SNAP-25. Agreements between simulations and experiments under both ensemble and single-molecule conditions allow us to assign specific helix-coil transitions in SNAP-25 that occur in sub-millisecond timescales and potentially play a vital role in forming the SNARE complex. We expect this integrative approach would help further our understanding of IDPs. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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