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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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Contribution ratios for the PC axes for each structural class. Contribution ratios (Q1, crosses; Q2, asterisks; and Q3, squares) of PCx1-PCx3 vs. segment lengths of 10–50 residues for each structural class, where x = α, β, α+β, or α/β. The correlation coefficient between PCxi and PCalli (i = 1, 2, 3) is 0.7 or less if no mark is present at a segment length. For the all-β class, no axis exhibited a correlation coefficient greater than 0.7 up to PCall3 for segment lengths of 10–16 residues.
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Figure 9: Contribution ratios for the PC axes for each structural class. Contribution ratios (Q1, crosses; Q2, asterisks; and Q3, squares) of PCx1-PCx3 vs. segment lengths of 10–50 residues for each structural class, where x = α, β, α+β, or α/β. The correlation coefficient between PCxi and PCalli (i = 1, 2, 3) is 0.7 or less if no mark is present at a segment length. For the all-β class, no axis exhibited a correlation coefficient greater than 0.7 up to PCall3 for segment lengths of 10–16 residues.

Mentions: Figure 9 depicts the contribution ratios of the first three PC axes, PCx1 -PCx3 (x = α, β, α +β, or α/β), in each structural class. The marks on the curves in Fig. 9 indicate that the correlation coefficient (vxi·valli) between PCx1 -PCx3 and PCall1 -PCall3 (i.e., i = 1, 2, 3) is greater than 0.7, which was used here as a threshold of conservation of structural properties. The properties of the first two PC axes corresponding to the PCall1 and PCall2 were highly conserved in all four structural classes. The characteristics of PCall3 were also conserved in all four structural classes, although exceptions were apparent for the 20-residue-long and 10–16-residue-long all-α and all-β classes. Therefore, it is confirmed that the first three PC axes (Rg, symmetry, and one/two turn(s)) are important in almost all cases to describe the conformation of segments embedded in globular proteins.


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

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

Contribution ratios for the PC axes for each structural class. Contribution ratios (Q1, crosses; Q2, asterisks; and Q3, squares) of PCx1-PCx3 vs. segment lengths of 10–50 residues for each structural class, where x = α, β, α+β, or α/β. The correlation coefficient between PCxi and PCalli (i = 1, 2, 3) is 0.7 or less if no mark is present at a segment length. For the all-β class, no axis exhibited a correlation coefficient greater than 0.7 up to PCall3 for segment lengths of 10–16 residues.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 9: Contribution ratios for the PC axes for each structural class. Contribution ratios (Q1, crosses; Q2, asterisks; and Q3, squares) of PCx1-PCx3 vs. segment lengths of 10–50 residues for each structural class, where x = α, β, α+β, or α/β. The correlation coefficient between PCxi and PCalli (i = 1, 2, 3) is 0.7 or less if no mark is present at a segment length. For the all-β class, no axis exhibited a correlation coefficient greater than 0.7 up to PCall3 for segment lengths of 10–16 residues.
Mentions: Figure 9 depicts the contribution ratios of the first three PC axes, PCx1 -PCx3 (x = α, β, α +β, or α/β), in each structural class. The marks on the curves in Fig. 9 indicate that the correlation coefficient (vxi·valli) between PCx1 -PCx3 and PCall1 -PCall3 (i.e., i = 1, 2, 3) is greater than 0.7, which was used here as a threshold of conservation of structural properties. The properties of the first two PC axes corresponding to the PCall1 and PCall2 were highly conserved in all four structural classes. The characteristics of PCall3 were also conserved in all four structural classes, although exceptions were apparent for the 20-residue-long and 10–16-residue-long all-α and all-β classes. Therefore, it is confirmed that the first three PC axes (Rg, symmetry, and one/two turn(s)) are important in almost all cases to describe the conformation of segments embedded in globular proteins.

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