Alpha helix

Historical development

In the early 1930s, William Astbury showed that there were drastic changes in the H. S. Taylor,^[2] Maurice Huggins^[3] and Bragg and collaborators^[4] to propose models of keratin that resemble the modern α-helix.

Two key developments in the modeling of the modern α-helix were (1) the correct bond geometry, thanks to the peptide bonds; and (2) the relinquishing of the assumption of an integral number of residues per turn of the helix. The pivotal moment came in January 1948, when Pauling caught a cold and went to bed. Being bored, he drew a polypeptide chain of roughly correct dimensions on a strip of paper and folded it into a helix, being careful to maintain the planar peptide bonds. After a few attempts, he produced a model with physically plausible hydrogen bonds. Pauling then worked with Corey and Branson to confirm his model before publication.^[5]

Structure

Geometry and hydrogen bonding

 

The amino acids in an α helix are arranged in a right-handed helical structure, 5.4 Å (= 0.54 nm) wide. Each amino acid corresponds to a 100° turn in the helix (i.e., the helix has 3.6 residues per turn), and a translation of 1.5 Å (= 0.15 nm) along the helical axis. Most importantly, the molecular dynamics simulations of α-helical folding.

Residues in α-helices typically adopt backbone (φ, ψ) Ramachandran plot (of slope -1), ranging from (-90°, -15°) to (-35°, -70°). For comparison, the sum of the dihedral angles for a 3₁₀ helix is roughly -75°, whereas that for the π-helix is roughly -130°. The general formula for the rotation angle Ω per residue of any polypeptide helix with trans isomers is given by the equation^{[citation needed]}

The α-helix is tightly packed; there is almost no free space within the helix. The amino-acid side chains are on the outside of the helix, and point roughly "downwards" (i.e., towards the N-terminus), like the branches of an evergreen tree (Christmas tree effect). This directionality is sometimes used in preliminary, low-resolution electron-density maps to determine the direction of the protein backbone.

Stability

Helices observed in proteins can range from four to over forty residues long, but a typical helix contains about ten amino acids (about three turns). Short trifluoroethanol (TFE), oligopeptides readily adopt stable α-helical structure.

Experimental determination

Since the α-helix is defined by its hydrogen bonds, the most reliable experimental methods for determining an α-helix involve an atomic-resolution structure provided by NMR spectroscopy. In some cases, the individual hydrogen bonds can be observed directly as a small scalar coupling in NMR.

There are several lower-resolution methods for assigning general helical structure. The hydrogen-deuterium exchange). Finally, cryo electron microscopy is now capable of discerning individual α-helices within a protein, although their assignment to residues is still an active area of research.

Long homopolymers of amino acids often form helices (if soluble). Such long, isolated helices can also be detected by other methods, such as dielectric relaxation, flow birefringence and measurements of its diffusion constant. Strictly speaking, these methods only detect the characteristic prolate (long cigar-like) hydrodynamic shape of a helix, or its large dipole moment.

Amino-acid propensities

Different amino-acid sequences have different propensities for forming α-helical structure. glycine also tends to disrupt helices because its high conformational flexibility makes it entropically expensive to adopt the relatively constrained α-helical structure.

Dipole moment

A helix has an overall dipole moment caused by the aggregate effect of all the individual dipoles from the lysine. The N-terminal positive charge is commonly used to bind negatively charged ligands such as phosphate groups, which is especially effective because the backbone amides can serve as hydrogen bond donors.

Larger-scale assemblies

crystallography, is made up of about 70% α helix, with the rest being loops or disordered regions. In classifying proteins by their dominant fold, the Structural Classification of Proteins database maintains a category specifically for all-α proteins.

Coiled-coil α helices are highly stable forms in which two or more helices wrap around each other in a "supercoil" structure. cytochrome. The Rop protein, which promotes plasmid replication in bacteria, is an interesting case in which a single polypeptide forms a coiled-coil and two monomers assemble to form a four-helix bundle.

The amino acids that make up a particular helix can be plotted on a helical wheel, a representation that illustrates the orientations of the constituent amino acids. Often in solvent-exposed surface of the protein.

Functional roles

α helices have particular significance in DNA.

Helix-coil transition

Homopolymers of amino-acids (such as statistical mechanics of this transition can be modeled using an elegant transfer matrix method, characterized by two parameters: the propensity to initiate a helix and the propensity to extend a helix.

The α-helix in fine art

At least two artists have made explicit reference to the α-helix in their work, Julie Newdoll in painting and Julian Voss-Andreae in sculpture.

Bay-Area artist Julie Newdoll, who holds a degree in Microbiology, and a minor in art, has specialized in paintings inspired by microscopic images and molecules since 1990. Her painting "Rise of the Alpha Helix" (2003) features human figures arranged in an α helical arrangement. According to the artist, "the flowers reflect the various types of sidechains that each amino acid holds out to the world".

 

Julian Voss-Andreae is a German-born sculptor with degrees in experimental physics and sculpture. Since 2001 Voss-Andreae creates "protein sculptures"^[6] based on protein structure with the α-helix being one of his preferred objects. Voss-Andreae has made α-helix sculptures from diverse materials including bamboo and whole trees. A monument Voss-Andreae created in 2004 to celebrate the memory of Linus Pauling, the discoverer of the α-helix, is fashioned from a large steel beam rearranged in the structure of the α-helix. The 10' (3 m) tall, bright-red sculpture stands in front of Pauling's childhood home in Portland, Oregon.

See also

• Folding (chemistry)
• β sheet
• collagen helix
• poly-Pro helix
• secondary structure
• tertiary structure
• Davydov soliton

References and footnotes

Additional references

• Carl Branden and John Tooze. 1999. Introduction to Protein Structure 2nd ed. Garland Publishing: New York, NY.

• David Eisenberg, "The discovery of the α-helix and β-sheet, the principal structural features of proteins". Proceedings of the National Academy of Sciences USA. (2003). 100:11207-11210. http://www.pnas.org/cgi/content/full/100/20/11207

• John Kendrew et al. 1960. The structure of myoglobin: a three-dimensional Fourier synthesis and 2Â resolution. Nature 185: 422-7.

• Astbury WT and Woods HJ. (1931) "The Molecular Weights of Proteins", Nature, 127, 663-665.

• Astbury WT and Street A. (1931) "X-ray studies of the structures of hair, wool and related fibres. I. General", Trans. R. Soc. Lond., A230, 75-101.

• Astbury WT. (1933) "Some Problems in the X-ray Analysis of the Structure of Animal Hairs and Other Protein Fibers", Trans. Faraday Soc., 29, 193-211.

• Astbury WT and Woods HJ. (1934) "X-ray studies of the structures of hair, wool and related fibres. II. The molecular structure and elastic properties of hair keratin", Trans. R. Soc. Lond., A232, 333-394.

• Astbury WT and Sisson WA. (1935) "X-ray studies of the structures of hair, wool and related fibres. III. The configuration of the keratin molecule and its orientation in the biological cell", Proc. R. Soc. Lond., A150, 533-551.

• Neurath H. (1940) "Intramolecular folding of polypeptide chains in relation to protein structure", J. Phys. Chem., 44, 296-305.

• Taylor HS. (1942) "Large molecules through atomic spectacles", Proc. Am. Philos. Soc., 85, 1-12.

• Huggins M. (1943) "The structure of fibrous proteins", Chem. Rev., 32, 195-218.

• Bragg L, Kendrew JC and Perutz MF. (1950) "Polypeptide chain configurations in crystalline proteins", Proc. Roy. Soc., A203, 321.

• Pauling L, Corey RB and Branson HR. (1951) "The Structure of Proteins: Two Hydrogen-Bonded Helical Configurations of the Polypeptide Chain", Proc. Nat. Acad. Sci. Wash., 37, 205.

• Sugeta H and Miyazawa T. (1967) "General Method for Calculating Helical Parameters of Polymer Chains from Bond Lengths, Bond Angles, and Internal-Rotation Angles", Biopolymers, 5, 673-679.

• Wada A. (1976) "The α-helix as an electric macro-dipole", Adv. Biophys., 9, 1-63.

• Chothia C, Levitt M and Richardson D. (1977) "Structure of proteins:Packing of α-helices and pleated sheets", Proceedings of the National Academy of Science USA, 74, 4130-4134.

• Chothia C, Levitt M and Richardson D. (1981) "Helix to Helix Packing in Proteins", Journal of Molecular Biology, 145, 215-250.

• Hol WGJ. (1985) "The role of the α-helix dipole in protein function and structure", Prog. Biophys. Mol. Biol., 45, 149-195.

• Barlow DJ and Thornton JM. (1988) "Helix Geometry in Proteins", J. Mol. Biol., 201, 601-619.

• Murzin AG and Finkelstein AV. (1988) "General architecture of the α-helical globule", Journal of Molecular Biology, 204, 749-769.

Protein secondary structure
Helices:	α-helix | 310 helix | π-helix | Polyproline helix | Collagen helix
Extended:	α-strand
Supersecondary:	Helix-turn-helix | EF hand
Secondary structure propensities of amino acids
Helix-favoring:	Lysine
Extended-favoring:	Tryptophan
Disorder-favoring:	Aspartic acid
No preference:	Arginine
Tertiary structure→