Mapping Distinct Sequences of Structure Formation Differentiating Multiple Folding Pathways of a Small Protein
- 12 January 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 143 (3), 1447-1457
- https://doi.org/10.1021/jacs.0c11097
Abstract
To determine experimentally how the multiple folding pathways of a protein differ, in the order in which the structural parts are assembled, has been a long-standing challenge. To resolve whether structure formation during folding can progress in multiple ways, the complex folding landscape of monellin has been characterized, structurally and temporally, using the multisite time-resolved FRET methodology. After an initial heterogeneous polypeptide chain collapse, structure formation proceeds on parallel pathways. Kinetic analysis of the population evolution data across various protein segments provides a clear structural distinction between the parallel pathways. The analysis leads to a phenomenological model that describes how and when discrete segments acquire structure independently of each other in different subensembles of protein molecules. When averaged over all molecules, structure formation is seen to progress as α-helix formation, followed by core consolidation, then β-sheet formation, and last end-to-end distance compaction. Parts of the protein that are closer in the primary sequence acquire structure before parts separated by longer sequence.Funding Information
- Science and Engineering Research Board
- Tata Institute of Fundamental Research
- Department of Biotechnology , Ministry of Science and Technology
- Department of Science and Technology, Ministry of Science and Technology, India
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