20
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Discerning the structure and energy of multiple transition states in protein folding using psi-analysis.

      Journal of Molecular Biology
      Amino Acid Sequence, Binding Sites, In Vitro Techniques, Kinetics, Metals, chemistry, Models, Molecular, Molecular Sequence Data, Mutagenesis, Site-Directed, Protein Engineering, Protein Folding, Proteins, genetics, Thermodynamics, Ubiquitin

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          We quantify the degree to which folding occurs along a complex landscape with structurally distinct pathways using psi-analysis in combination with a protein engineering method that identifies native, non-covalent polypeptide interactions and their relative populations at the rate-limiting step. By probing the proximity of two specific partners, this method is extremely well-suited for comparison to theoretical simulations. Using ubiquitin as a model system, we detect individual pathways with site-resolved resolution, demonstrating that the protein folds through a native-like transition state ensemble with a common nucleus that contains heterogeneous features on its periphery. The consensus transition state topology has part of the major helix docked against four properly aligned beta-strands. However, structural heterogeneity exists in the transition state ensemble, wherein peripheral regions are differentially populated according to their relative stability. Pathway diversity reflects the variable order of formation of these peripheral elements, which radiate outward from the common nucleus. These results, which show only moderate agreement with traditional mutational phi-analysis, provide an extraordinarily detailed and quantitative description of protein folding.

          Related collections

          Author and article information

          Comments

          Comment on this article