Mapping Distinct Sequences of Structure Formation Differentiating Multiple Folding Pathways of a Small Protein.
Title | Mapping Distinct Sequences of Structure Formation Differentiating Multiple Folding Pathways of a Small Protein. |
Publication Type | Journal Article |
Year of Publication | 2021 |
Authors | Bhatia S, Krishnamoorthy G, Udgaonkar JB |
Journal | J Am Chem Soc |
Date Published | 2021 Jan 12 |
ISSN | 1520-5126 |
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. |
DOI | 10.1021/jacs.0c11097 |
Alternate Journal | J Am Chem Soc |
PubMed ID | 33430589 |