Abstract
The charge-containing hydrophilic functionalities of encoded charged amino acids are linked to the backbone via different numbers of hydrophobic methylenes, despite the apparent electrostatic nature of protein ion pairing interactions. To investigate the effect of side chain length of guanidinium- and carboxylate-containing residues on ion pairing interactions, α-helical peptides containing Zbb–Xaa (i, i + 3), (i, i + 4) and (i, i + 5) (Zbb = carboxylate-containing residues Aad, Glu, Asp in decreasing length; Xaa = guanidinium residues Agh, Arg, Agb, Agp in decreasing length) sequence patterns were studied by circular dichroism spectroscopy (CD). The helicity of Aad- and Glu-containing peptides was similar and mostly pH independent, whereas the helicity of Asp-containing peptides was mostly pH dependent. Furthermore, the Arg-containing peptides consistently exhibited higher helicity compared to the corresponding Agp-, Agb-, and Agh-containing peptides. Side chain conformational analysis by molecular mechanics calculations showed that the Zbb–Xaa (i, i + 3) and (i, i + 4) interactions mainly involved the χ 1 dihedral combinations (g+, g+) and (g−, g+), respectively. These low energy conformations were also observed in intrahelical Asp–Arg and Glu–Arg salt bridges of natural proteins. Accordingly, Asp and Glu provides variation in helix characteristics associated with Arg, but Aad does not provide features beyond those already delivered by Glu. Importantly, nature may have chosen the side chain length of Arg to support helical conformations through inherent high helix propensity coupled with stabilizing intrahelical ion pairing interactions with the carboxylate-containing residues.
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Abbreviations
- Aad:
-
(S)-aminoadipate
- Agb:
-
(S)-2-amino-4-guanidinobutyric acid
- Agh:
-
(S)-2-amino-6-guanidinohexanoic acid
- Agp:
-
(S)-2-amino-3-guanidinopropionic acid
- Ala:
-
Alanine
- Arg:
-
Arginine
- Asp:
-
Aspartate
- CD:
-
Circular dichroism spectroscopy
- Fmoc:
-
N α-fluorenylmethyloxycarbonyl
- Glu:
-
Glutamate
- Lys:
-
Lysine
- MALDI-TOF:
-
Matrix-assisted laser desorption ionization time-of-flight
- Tyr:
-
Tyrosine
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Acknowledgments
This work was supported by National Taiwan University (NTU-ERP-103R891302) and the Ministry of Science and Technology in Taiwan (former National Science Council; NSC-97-2113-111-002-019-MY2, NSC-98-2119-M-002-025, NSC-99-2113-M-002-002-MY2, NSC-101-2113-M-002-006-MY2). The authors would like to thank the Computer and Information Networking Center at National Taiwan University for the support of the high-performance computing facilities.
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Kuo, HT., Yang, PA., Wang, WR. et al. Effect of side chain length on intrahelical interactions between carboxylate- and guanidinium-containing amino acids. Amino Acids 46, 1867–1883 (2014). https://doi.org/10.1007/s00726-014-1737-8
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DOI: https://doi.org/10.1007/s00726-014-1737-8