Dataset Information

Nonnative Energetic Frustrations in Protein Folding at Residual Level: A Simulation Study of Homologous Immunoglobulin-like ?-Sandwich Proteins.

ABSTRACT: Nonnative interactions cause energetic frustrations in protein folding and were found to dominate key events in folding intermediates. However, systematically characterizing energetic frustrations that are caused by nonnative intra-residue interactions at residual resolution is still lacking. Recently, we studied the folding of a set of homologous all-? proteins and found that nonnative-contact-based energetic frustrations are highly correlated to topology of the protein native-contact network. Here, we studied the folding of nine homologous immunoglobulin-like (Ig-like) ?-sandwich proteins, and examined nonnative-contact-based energetic frustrations G?-like model. Our calculations showed that nonnative-interaction-based energetic frustrations in ?-sandwich proteins are much more complicated than those in all- ? proteins, and they exhibit highly heterogeneous effects on the folding of secondary structures. Further, the nonnative interactions introduced distinct correlations in the folding of different folding-patches of ?-sandwich proteins. Taken together, a strong interplay might exist between nonnative-interaction energetic frustrations and the protein native-contact networks, which ensures that ?-sandwich domains adopt a common folding mechanism.

SUBMITTER: Sun Y

PROVIDER: S-EPMC5983731 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

Nonnative Energetic Frustrations in Protein Folding at Residual Level: A Simulation Study of Homologous Immunoglobulin-like <i>β</i>-Sandwich Proteins.

Sun Yunxiang Y Ding Feng F Ming Dengming D

International journal of molecular sciences 20180518 5

Nonnative interactions cause energetic frustrations in protein folding and were found to dominate key events in folding intermediates. However, systematically characterizing energetic frustrations that are caused by nonnative intra-residue interactions at residual resolution is still lacking. Recently, we studied the folding of a set of homologous all-<i>α</i> proteins and found that nonnative-contact-based energetic frustrations are highly correlated to topology of the protein native-contact ne ...[more]

PMID: 29783701

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Project description:The thermodynamic hypothesis of Anfinsen postulates that structures and stabilities of globular proteins are determined by their amino acid sequences. Chain topology, however, is known to influence the folding reaction, in that motifs with a preponderance of local interactions typically fold more rapidly than those with a larger fraction of nonlocal interactions. Together, the topology and sequence can modulate the energy landscape and influence the rate at which the protein folds to the native conformation. To explore the relationship of sequence and topology in the folding of beta alpha-repeat proteins, which are dominated by local interactions, we performed a combined experimental and simulation analysis on two members of the flavodoxin-like, alpha/beta/alpha sandwich fold. Spo0F and the N-terminal receiver domain of NtrC (NT-NtrC) have similar topologies but low sequence identity, enabling a test of the effects of sequence on folding. Experimental results demonstrated that both response-regulator proteins fold via parallel channels through highly structured submillisecond intermediates before accessing their cis prolyl peptide bond-containing native conformations. Global analysis of the experimental results preferentially places these intermediates off the productive folding pathway. Sequence-sensitive G?-model simulations conclude that frustration in the folding in Spo0F, corresponding to the appearance of the off-pathway intermediate, reflects competition for intra-subdomain van der Waals contacts between its N- and C-terminal subdomains. The extent of transient, premature structure appears to correlate with the number of isoleucine, leucine, and valine (ILV) side chains that form a large sequence-local cluster involving the central beta-sheet and helices alpha2, alpha 3, and alpha 4. The failure to detect the off-pathway species in the simulations of NT-NtrC may reflect the reduced number of ILV side chains in its corresponding hydrophobic cluster. The location of the hydrophobic clusters in the structure may also be related to the differing functional properties of these response regulators. Comparison with the results of previous experimental and simulation analyses on the homologous CheY argues that prematurely folded unproductive intermediates are a common property of the beta alpha-repeat motif.

Dataset Information

Nonnative Energetic Frustrations in Protein Folding at Residual Level: A Simulation Study of Homologous Immunoglobulin-like ?-Sandwich Proteins.

Publications

Nonnative Energetic Frustrations in Protein Folding at Residual Level: A Simulation Study of Homologous Immunoglobulin-like <i>β</i>-Sandwich Proteins.

Similar Datasets

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