Cited 9 time in
Cited 9 time in
Even with nonnative interactions, the updated folding transition states of the homologs Proteins G & L are extensive and similar
- Even with nonnative interactions, the updated folding transition states of the homologs Proteins G & L are extensive and similar
- 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
- Proceedings of the National Academy of Sciences of the United States of America, 112(27), 8302-8307
- Article Type
- Algorithm; Algorithms; Amino Acid Sequence; Bi-Histidine; Binding Affinity; Chemistry; Comparative Study; Controlled Study; Genetics; Kinetics; Molecular Dynamics; Molecular Dynamics Simulation; Molecular Genetics; Molecular Sequence Data; Mutation; NuG2b Protein; Phi Analysis; Priority Journal; Protein; Protein Analysis; Protein Binding; Protein Conformation; Protein Folding; Protein G; Protein Interaction; Protein L; Protein Localization; Protein Secondary Structure; Protein Structure, Secondary; Proteins; PSI Analysis; Thermodynamics; Transition State Ensemble; Unclassified Drug
- 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.
- National Academy of Sciences
- Related Researcher
Laboratory of Protein Biophysics
protein biophysics; protein folding; protein dynamics and conformational change
There are no files associated with this item.
- Department of Brain and Cognitive SciencesLaboratory of Protein Biophysics1. Journal Articles
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.