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Protein-segment universe exhibiting transitions at intermediate segment length in conformational subspaces.

Ikeda K, Hirokawa T, Higo J, Tomii K - BMC Struct. Biol. (2008)

Bottom Line: Those characteristics suggest that protein segment conformation is described by compositions of the three common structural variables with large contributions and specific structural variables with small contributions.The present results of the analyses of four protein structural classes show the universal role of three major components as segment conformational descriptors.The obtained perspectives of distribution changes related to the segment lengths using the three key components suggest both the adequacy and the possibility of further progress on the prediction strategies used in the recent de novo structure-prediction methods.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, 2-42 Aomi, Koto-ku, Tokyo 135-0064, Japan. ikeda@pharmadesign.co.jp

ABSTRACT

Background: Many studies have examined rules governing two aspects of protein structures: short segments and proteins' structural domains. Nevertheless, the organization and nature of the conformational space of segments with intermediate length between short segments and domains remain unclear. Conformational spaces of intermediate length segments probably differ from those of short segments. We investigated the identification and characterization of the boundary(s) between peptide-like (short segment) and protein-like (long segment) distributions. We generated ensembles embedded in globular proteins comprising segments 10-50 residues long. We explored the relationships between the conformational distribution of segments and their lengths, and also protein structural classes using principal component analysis based on the intra-segment Calpha-Calpha atomic distances.

Results: Our statistical analyses of segment conformations and length revealed critical dual transitions in their conformational distribution with segments derived from all four structural classes. Dual transitions were identified with the intermediate phase between the short segments and domains. Consequently, protein segment universes were categorized. i) Short segments (10-22 residues) showed a distribution with a high frequency of secondary structure clusters. ii) Medium segments (23-26 residues) showed a distribution corresponding to an intermediate state of transitions. iii) Long segments (27-50 residues) showed a distribution converging on one huge cluster containing compact conformations with a smaller radius of gyration. This distribution reflects the protein structures' organization and protein domains' origin. Three major conformational components (radius of gyration, structural symmetry with respect to the N-terminal and C-terminal halves, and single-turn/two-turn structure) well define most of the segment universes. Furthermore, we identified several conformational components that were unique to each structural class. Those characteristics suggest that protein segment conformation is described by compositions of the three common structural variables with large contributions and specific structural variables with small contributions.

Conclusion: The present results of the analyses of four protein structural classes show the universal role of three major components as segment conformational descriptors. The obtained perspectives of distribution changes related to the segment lengths using the three key components suggest both the adequacy and the possibility of further progress on the prediction strategies used in the recent de novo structure-prediction methods.

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Correlation coefficients between conformational deviation along each PC axis and physical indicator. The radius of gyration (Rg) for PCall1, structural symmetry related to the N-terminal and C-terminal halves (Dsim) for PCall2, a simple indicator of β-hairpin (Dmn+mc) and Dmn+mc/end-to-end distance (Dend) for PCall3, and the radius of gyration (midRg) around the midpoint of the segment for PCall4 were used in these analyses. Correlation coefficients were calculated at every 10 residues of 10–50 residues.
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Figure 8: Correlation coefficients between conformational deviation along each PC axis and physical indicator. The radius of gyration (Rg) for PCall1, structural symmetry related to the N-terminal and C-terminal halves (Dsim) for PCall2, a simple indicator of β-hairpin (Dmn+mc) and Dmn+mc/end-to-end distance (Dend) for PCall3, and the radius of gyration (midRg) around the midpoint of the segment for PCall4 were used in these analyses. Correlation coefficients were calculated at every 10 residues of 10–50 residues.

Mentions: Actually, PCall1 corresponds to the change of the radius of gyration (Rg). The triangle map for PCall1 has only one positive area, shown as red in Fig. 6, which is located near the residue pairs at the N-terminal and C-terminal sides. This single area indicates that the distant residue pairs in the sequence have a larger conformational deviation along PCall1. The correlation coefficient of the conformational deviation along PCall1 with Rg was greater than 0.9 in segment lengths of 10–50 residues (Fig. 8). The arrows in Fig. 7 point to the center of the segment, which indicates clearly that the conformational changes along PCall1 are involved with expansions or compressions of the conformation. For short lengths, PCall1 also shows a strong correlation with the changes of the segment end-to-end distance (Dend), which is defined as the Cα-Cα distance between the first and last residues of segments. Correlation between PCall1 and Dend slowly weakened with increased segment length: 0.91 for 10 residues, 0.79 for 26 residues, and 0.77 for 30 residues.


Protein-segment universe exhibiting transitions at intermediate segment length in conformational subspaces.

Ikeda K, Hirokawa T, Higo J, Tomii K - BMC Struct. Biol. (2008)

Correlation coefficients between conformational deviation along each PC axis and physical indicator. The radius of gyration (Rg) for PCall1, structural symmetry related to the N-terminal and C-terminal halves (Dsim) for PCall2, a simple indicator of β-hairpin (Dmn+mc) and Dmn+mc/end-to-end distance (Dend) for PCall3, and the radius of gyration (midRg) around the midpoint of the segment for PCall4 were used in these analyses. Correlation coefficients were calculated at every 10 residues of 10–50 residues.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2529298&req=5

Figure 8: Correlation coefficients between conformational deviation along each PC axis and physical indicator. The radius of gyration (Rg) for PCall1, structural symmetry related to the N-terminal and C-terminal halves (Dsim) for PCall2, a simple indicator of β-hairpin (Dmn+mc) and Dmn+mc/end-to-end distance (Dend) for PCall3, and the radius of gyration (midRg) around the midpoint of the segment for PCall4 were used in these analyses. Correlation coefficients were calculated at every 10 residues of 10–50 residues.
Mentions: Actually, PCall1 corresponds to the change of the radius of gyration (Rg). The triangle map for PCall1 has only one positive area, shown as red in Fig. 6, which is located near the residue pairs at the N-terminal and C-terminal sides. This single area indicates that the distant residue pairs in the sequence have a larger conformational deviation along PCall1. The correlation coefficient of the conformational deviation along PCall1 with Rg was greater than 0.9 in segment lengths of 10–50 residues (Fig. 8). The arrows in Fig. 7 point to the center of the segment, which indicates clearly that the conformational changes along PCall1 are involved with expansions or compressions of the conformation. For short lengths, PCall1 also shows a strong correlation with the changes of the segment end-to-end distance (Dend), which is defined as the Cα-Cα distance between the first and last residues of segments. Correlation between PCall1 and Dend slowly weakened with increased segment length: 0.91 for 10 residues, 0.79 for 26 residues, and 0.77 for 30 residues.

Bottom Line: Those characteristics suggest that protein segment conformation is described by compositions of the three common structural variables with large contributions and specific structural variables with small contributions.The present results of the analyses of four protein structural classes show the universal role of three major components as segment conformational descriptors.The obtained perspectives of distribution changes related to the segment lengths using the three key components suggest both the adequacy and the possibility of further progress on the prediction strategies used in the recent de novo structure-prediction methods.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, 2-42 Aomi, Koto-ku, Tokyo 135-0064, Japan. ikeda@pharmadesign.co.jp

ABSTRACT

Background: Many studies have examined rules governing two aspects of protein structures: short segments and proteins' structural domains. Nevertheless, the organization and nature of the conformational space of segments with intermediate length between short segments and domains remain unclear. Conformational spaces of intermediate length segments probably differ from those of short segments. We investigated the identification and characterization of the boundary(s) between peptide-like (short segment) and protein-like (long segment) distributions. We generated ensembles embedded in globular proteins comprising segments 10-50 residues long. We explored the relationships between the conformational distribution of segments and their lengths, and also protein structural classes using principal component analysis based on the intra-segment Calpha-Calpha atomic distances.

Results: Our statistical analyses of segment conformations and length revealed critical dual transitions in their conformational distribution with segments derived from all four structural classes. Dual transitions were identified with the intermediate phase between the short segments and domains. Consequently, protein segment universes were categorized. i) Short segments (10-22 residues) showed a distribution with a high frequency of secondary structure clusters. ii) Medium segments (23-26 residues) showed a distribution corresponding to an intermediate state of transitions. iii) Long segments (27-50 residues) showed a distribution converging on one huge cluster containing compact conformations with a smaller radius of gyration. This distribution reflects the protein structures' organization and protein domains' origin. Three major conformational components (radius of gyration, structural symmetry with respect to the N-terminal and C-terminal halves, and single-turn/two-turn structure) well define most of the segment universes. Furthermore, we identified several conformational components that were unique to each structural class. Those characteristics suggest that protein segment conformation is described by compositions of the three common structural variables with large contributions and specific structural variables with small contributions.

Conclusion: The present results of the analyses of four protein structural classes show the universal role of three major components as segment conformational descriptors. The obtained perspectives of distribution changes related to the segment lengths using the three key components suggest both the adequacy and the possibility of further progress on the prediction strategies used in the recent de novo structure-prediction methods.

Show MeSH
Related in: MedlinePlus