310 helix

Side view of a 310-helix of alanine residues in atomic detail. Two hydrogen bonds to the same peptide group are highlighted in magenta; the oxygen-hydrogen distance is 1.83 Å (183 pm). The protein chain runs upwards, i.e., its N-terminus is at the bottom and its C-terminus at the top of the figure. Note that the sidechains point slightly downwards, i.e., towards the N-terminus.

A 310 helix is a type of secondary structure found in proteins and polypeptides. Of the countless protein secondary structures present, the 310-helix is the fourth most common type observed; following α-helices, β-sheets and reverse turns. 310-helices constitute nearly 10–15% of all helices in protein secondary structures, and are typically observed as extensions of α-helices found at either their N- or C- termini. Because of the α-helices tendency to consistently fold and unfold, it has been proposed that the 310-helix serves as an intermediary conformation of sorts, and provides insight into the initiation of α-helix folding.

Top view of the same helix shown to the right. Three carbonyl groups are pointing upwards towards the viewer, spaced roughly 120° apart on the circle, corresponding to 3.0 amino-acid residues per turn of the helix.

Discovery

It was Max Perutz, the head of the Medical Research Council at the University of Cambridge, who first wrote the first paper documenting the elusive 310-helix.[1] Together with Lawrence Bragg and John Kendrew, Perutz published an exploration of polypeptide chain configurations in 1950.[2] Their proposals missed the two most common structural motifs now known to occur. The following year, Linus Pauling predicted both of these motifs, the alpha helix[3] and the beta sheet,[4] in work which is now compared in significance[1] to Francis Crick and James D. Watson's publication of the DNA double helix.[5] Pauling was highly critical of the helical structures proposed by Bragg, Kendrew, and Perutz, taking a triumphal tone in declaring them all implausible.[1][3] Perutz describes in his book I wish I'd made you angry sooner[6] the experience of reading Pauling's paper one Saturday morning:

I was thunderstruck by Pauling and Corey's paper. In contrast to Kendrew's and my helices, theirs was free of strain; all of the amide groups were planar and every carbonyl group formed a perfect hydrogen bond with an imino group four residues further along the chain. The structure looked dead right. How could I have missed it?
— Max Perutz, 1998, pp.173-175.[6]

Later that day, an idea for an experiment to confirm Pauling's model occurred to Perutz, and he rushed to the lab to carry it out. Within a few hours, he had the evidence to confirm the alpha helix, which he showed to Bragg first thing on Monday.[1] Perutz' confirmation of the alpha helix structure was published in Nature.[7]

In his paper, Perutz analysed secondary structural cues from noncrystalline diffraction data as well as from small molecule crystal structures such as collagen found in hair. His findings regarding the theoretical configurations of polypeptides were as follows:

Structure

The amino acids in a 310-helix are arranged in a right-handed helical structure. Each amino acid corresponds to a 120° turn in the helix (i.e., the helix has three residues per turn), and a translation of 2.0 Å (0.20 nm) along the helical axis, and has 10 atoms in the ring formed by making the hydrogen bond. Most importantly, the N-H group of an amino acid forms a hydrogen bond with the C=O group of the amino acid three residues earlier; this repeated i + 3 → i hydrogen bonding defines a 310-helix. Similar structures include the α-helix (i + 4 → i hydrogen bonding) and the π-helix i + 5 → i hydrogen bonding.

Residues in long 310-helices adopt (φ, ψ) dihedral angles near (−49°, −26°). Many 310-helices in proteins are short, so deviate from these values. More generally, residues in long 310-helices adopt dihedral angles such that the ψ dihedral angle of one residue and the φ dihedral angle of the next residue sum to roughly −75°. For comparison, the sum of the dihedral angles for an α-helix is roughly −105°, whereas that for a π-helix is roughly −125°.

The general formula for the rotation angle Ω per residue of any polypeptide helix with trans isomers is given by the equation

The (−49°, −26°) (φ, ψ) dihedral angles could be attributed to the short lengths of these helices, ranging anywhere from 3 to 5 residues long, compared to the 10 to 12 residue lengths of their α-helix contemporaries. Short residue lengths can cause deviations in their main-chain torsion angle distributions, accounting for their irregularity. Scientists’ theory behind the instability of 310-helices arises from their small lengths, as well as the fact that they constitute a distorted hydrogen bond network, though the frequency of the 310-helix in nature suggests that it serves an ample purpose.

Stability

Through research carried out by Mary Karpen, Pieter De Haseth and Kenneth Neet, new findings in the partial stability in 310-helices were uncovered. The helices are most noticeably stabilized by an aspartate residue at the nonpolar N-terminus that interacts with the amide group at the helical N-cap. This electrostatic interaction stabilizes the peptide dipoles in a parallel orientation. Much like the contiguous helical hydrogen bonds that stabilize α-helices, high levels of aspartate are just as equally important in the survival of the 310-helix. High frequency of aspartate in both 310-helix and α-helices is indicative of its helix initiation, but at the same time suggests that it favors stabilization of the 310-helix by inhibiting the propagation of α-helices.

See also

References

  1. 1 2 3 4 Eisenberg, David (2003). "The discovery of the α-helix and β-sheet, the principal structural features of proteins". Proc. Natl. Acad. Sci. U.S.A. 100 (20):  11207–11210. doi:10.1073/pnas.2034522100 Freely accessible.
  2. ↑ Bragg, Lawrence; Kendrew, J. C.; Perutz, M. F. (1950). "Polypeptide chain configurations in crystalline proteins". Proc. R. Soc. A. 203 (1074): 321–357. doi:10.1098/rspa.1950.0142 Freely accessible.
  3. 1 2 Pauling, Linus; Corey, Robert B.; Branson, Herman R. (1951). "The structure of proteins: Two hydrogen-bonded helical configurations of the polypeptide chain". Proc. Natl. Acad. Sci. U.S.A. 34 (4): 205–211. doi:10.1073/pnas.37.4.205 Freely accessible.
  4. ↑ Pauling, Linus; Corey, Robert B. (1951). "The Pleated Sheet, A New Layer Configuration of Polypeptide Chains" (PDF). Proc. Natl. Acad. Sci. U.S.A. 37 (5): 251–256.
  5. ↑ Watson, James D.; Crick, Francis H. C. (1953). "Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid". Nature. 171 (4356): 737–738. PMID 13054692. doi:10.1038/171737a0 Freely accessible.
  6. 1 2 Perutz, Max F. (1998). I Wish I'd Made You Angry Earlier: Essays on Science, Scientists, and Humanity. Plainview: Cold Spring Harbor Laboratory Press. ISBN 9780879696740.
  7. ↑ Perutz, Max F. (1951). "New X-Ray Evidence on the Configuration of Polypeptide Chains: Polypeptide Chains in Poly-γ-benzyl-L-glutamate, Keratin and Hæmoglobin". Nature. 167 (4261): 1053–1054. doi:10.1038/1671053a0.

Other readings

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.