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Even with nonnative interactions, the updated folding transition states of the homologs Proteins G & L are extensive and similar

Title
Even with nonnative interactions, the updated folding transition states of the homologs Proteins G & L are extensive and similar
Authors
Baxa, MC[Baxa, Michael C.]Yu, W[Yu, Wookyung]Adhikari, AN[Adhikari, Aashish N.]Ge, L[Ge, Liang]Xia, Z[Xia, Zhen]Zhou, RH[Zhou, Ruhong]Freed, KF[Freed, Karl F.]Sosnick, TR[Sosnick, Tobin R.]
DGIST Authors
Yu, W[Yu, Wookyung]
Issue Date
2015-07-07
Citation
Proceedings of the National Academy of Sciences of the United States of America, 112(27), 8302-8307
Type
Article
Article Type
Article
Keywords
AlgorithmAlgorithmsAmino Acid SequenceBi-HistidineBinding AffinityChemistryComparative StudyControlled StudyGeneticsKineticsMolecular DynamicsMolecular Dynamics SimulationMolecular GeneticsMolecular Sequence DataMutationNuG2b ProteinPhi AnalysisPriority JournalProteinProtein AnalysisProtein BindingProtein ConformationProtein FoldingProtein GProtein InteractionProtein LProtein LocalizationProtein Secondary StructureProtein Structure, SecondaryProteinsPSI AnalysisThermodynamicsTransition State EnsembleUnclassified Drug
ISSN
0027-8424
Abstract
Experimental and computational folding studies of Proteins L & G and NuG2 typically find that sequence differences determine which of the two hairpins is formed in the transition state ensemble (TSE). However, our recent work on Protein L finds that its TSE contains both hairpins, compelling a reassessment of the influence of sequence on the folding behavior of the other two homologs. We characterize the TSEs for Protein G and NuG2b, a triple mutant of NuG2, using ψ analysis, a method for identifying contacts in the TSE. All three homologs are found to share a common and near-native TSE topology with interactions between all four strands. However, the helical content varies in the TSE, being largely absent in Proteins G & L but partially present in NuG2b. The variability likely arises from competing propensities for the formation of nonnative β turns in the naturally occurring proteins, as observed in our TerItFix folding algorithm. All-atom folding simulations of NuG2b recapitulate the observed TSEs with four strands for 5 of 27 transition paths [Lindorff- Larsen K, Piana S, Dror RO, Shaw DE (2011) Science 334 (6055):517-520]. Our data support the view that homologous proteins have similar folding mechanisms, even when nonnative interactions are present in the transition state. These findings emphasize the ongoing challenge of accurately characterizing and predicting TSEs, even for relatively simple proteins.
URI
http://hdl.handle.net/20.500.11750/2878
DOI
10.1073/pnas.1503613112
Publisher
National Academy of Sciences
Related Researcher
  • Author Yu, Woo Kyung Laboratory of Protein Biophysics
  • Research Interests protein biophysics; protein folding; protein dynamics and conformational change
Files:
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Collection:
Brain and Cognitive SciencesETC1. Journal Articles


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