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Stereochemistry of residues in turning regions of helical proteins

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Abstract

We have developed a geometrical approach to quantify differences in the stereochemistry of α-helical and turning regions in four iron proteins. Two spatial signatures are used to analyze residue coordinate data for each protein; and a third is employed to analyze amino-acid molecular volume data. The residue-by-residue analysis of the results, taken together with the finding that two major factors stabilize an α-helix (minimization of side-chain steric interference and intrachain H-bonding), lead to the conclusion that certain residues are preferentially selected for α-helix formation. In the sequential, de novo synthesis of a turning region, residues are preferentially selected such that the overall molecular volume profile (representing purely repulsive, excluded-volume effects) spans a small range Δ of values (Δ = 39.1 Å3) relative to the total range that could be spanned (Δ = 167.7 Å3). It follows that excluded-volume effects are of enormous importance for residues in helical regions as well as those in adjacent turning regions. Once steric effects are taken into account, down-range attractive interactions between residues come into play in the formation of α-helical regions. The geometry of α-helices can be accommodated by conformational changes in less-structured turning regions of a polypeptide, thereby producing a globally optimized (native) protein structure.

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Acknowledgments

Work at Caltech was supported by the National Institutes of Health (DK-019038 to HBG).

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Authors and Affiliations

  1. Department of Chemistry, DePaul University, Chicago, IL, 60604-6116, USA

    John J. Kozak

  2. Beckman Institute, California Institute of Technology, Pasadena, CA, 91125, USA

    Harry B. Gray

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  1. John J. Kozak
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  2. Harry B. Gray
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Correspondence to Harry B. Gray.

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Appendices

Appendices

Appendix 1

See Figs. 9, 10, 11, 12.

Fig. 9
figure 9

Ratio T(i)/R(i − 2) to R(i + 2) vs residue number for cyt c’

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Fig. 10
figure 10

Ratio T(i)/R(i − 2) to R(i + 2) vs residue number for sw-Mb

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Fig. 11
figure 11

Difference R(i − 2) to R(i + 2) − T(i) vs residue number for cyt c’

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Fig. 12
figure 12

Difference R(i − 2) to R(i + 2) − T(i) vs residue number for sw-Mb

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Appendix 2

See Tables 4, 5, 6, 7.

Table 4 Residues in turning regions of cyt c-b562
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Table 5 Residues in turning regions of cyt c’
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Table 6 Residues in turning regions of sw-Mb
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Table 7 Residues in turning regions of h-Mb
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Kozak, J.J., Gray, H.B. Stereochemistry of residues in turning regions of helical proteins. J Biol Inorg Chem 24, 879–888 (2019). https://doi.org/10.1007/s00775-019-01696-9

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