0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Analyses of the folding sites of irregular β-trefoil fold proteins through sequence-based techniques and Gō-model simulations

      Read this article at

      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

          Background

          The details of the folding mechanisms have not yet been fully understood for many proteins, and it is believed that the information on the folding mechanism of a protein is encoded in its amino acid sequence. β-trefoil proteins are known to have the same 3D scaffold, namely, a three-fold symmetric scaffold, despite the proteins’ low sequence identity among superfamilies. In this study, we extract an initial folding unit from the amino acid sequences of irregular β-trefoil proteins by constructing an average distance map (ADM) and utilizing inter-residue average distance statistics to determine the relative contact frequencies for residue pairs in terms of F values. We compare our sequence-based prediction results with the packing between hydrophobic residues in native 3D structures and a Gō-model simulation.

          Results

          The ADM and F-value analyses predict that the N-terminal and C-terminal regions are compact and that the hydrophobic residues at the central region can be regarded as an interaction center with other residues. These results correspond well to those of the Gō-model simulations. Moreover, our results indicate that the irregular parts in the β-trefoil proteins do not hinder the protein formation. Conserved hydrophobic residues on the β5 strand are always the interaction center of packing between the conserved hydrophobic residues in both regular and irregular β-trefoil proteins.

          Conclusions

          We revealed that the β5 strand plays an important role in β-trefoil protein structure construction. The sequence-based methods used in this study can extract the protein folding information from only amino acid sequence data, and well corresponded to 3D structure-based Gō-model simulation and available experimental results.

          Related collections

          Most cited references 34

          • Record: found
          • Abstract: found
          • Article: not found

          Protein folding and misfolding.

           C Dobson (2003)
          The manner in which a newly synthesized chain of amino acids transforms itself into a perfectly folded protein depends both on the intrinsic properties of the amino-acid sequence and on multiple contributing influences from the crowded cellular milieu. Folding and unfolding are crucial ways of regulating biological activity and targeting proteins to different cellular locations. Aggregation of misfolded proteins that escape the cellular quality-control mechanisms is a common feature of a wide range of highly debilitating and increasingly prevalent diseases.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Protein structure alignment by incremental combinatorial extension (CE) of the optimal path.

            A new algorithm is reported which builds an alignment between two protein structures. The algorithm involves a combinatorial extension (CE) of an alignment path defined by aligned fragment pairs (AFPs) rather than the more conventional techniques using dynamic programming and Monte Carlo optimization. AFPs, as the name suggests, are pairs of fragments, one from each protein, which confer structure similarity. AFPs are based on local geometry, rather than global features such as orientation of secondary structures and overall topology. Combinations of AFPs that represent possible continuous alignment paths are selectively extended or discarded thereby leading to a single optimal alignment. The algorithm is fast and accurate in finding an optimal structure alignment and hence suitable for database scanning and detailed analysis of large protein families. The method has been tested and compared with results from Dali and VAST using a representative sample of similar structures. Several new structural similarities not detected by these other methods are reported. Specific one-on-one alignments and searches against all structures as found in the Protein Data Bank (PDB) can be performed via the Web at http://cl.sdsc.edu/ce.html.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Topological and energetic factors: what determines the structural details of the transition state ensemble and "en-route" intermediates for protein folding? An investigation for small globular proteins.

              Recent experimental results suggest that the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble, at least for small, fast-folding proteins. To investigate the extent of the topological control of the folding process, we studied the folding of simplified models of five small globular proteins constructed using a Go-like potential to retain the information about the native structures but drastically reduce the energetic frustration and energetic heterogeneity among residue-residue native interactions. By comparing the structure of the transition state ensemble (experimentally determined by Phi-values) and of the intermediates with those obtained using our models, we show that these energetically unfrustrated models can reproduce the global experimentally known features of the transition state ensembles and "en-route" intermediates, at least for the analyzed proteins. This result clearly indicates that, as long as the protein sequence is sufficiently minimally frustrated, topology plays a central role in determining the folding mechanism. Copyright 2000 Academic Press.
                Bookmark

                Author and article information

                Contributors
                tkikuchi@sk.ritsumei.ac.jp
                Journal
                BMC Mol Cell Biol
                BMC Mol Cell Biol
                BMC Molecular and Cell Biology
                BioMed Central (London )
                2661-8850
                21 July 2020
                21 July 2020
                2020
                : 21
                Affiliations
                [1 ]GRID grid.262576.2, ISNI 0000 0000 8863 9909, Department of Bioinformatics, College of Life Sciences, , Ritsumeikan University, ; 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 Japan
                [2 ]GRID grid.419250.b, National Center for Genetic Engineering and Biotechnology (BIOTEC), ; 113 Thailand Science Park, Phaholyothin Road, Klong Luang, Pathumthani 12120 Thailand
                Article
                271
                10.1186/s12860-020-00271-4
                7477875
                32295515
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001700, Ministry of Education, Culture, Sports, Science and Technology;
                Award ID: S1511028
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Comments

                Comment on this article