Alpha helix - Knowledge

318:; and his relinquishing of the assumption of an integral number of residues per turn of the helix. The pivotal moment came in the early spring of 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. In 1954, Pauling was awarded his first Nobel Prize "for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances" (such as proteins), prominently including the structure of the α-helix. 587: 113: 583:(TFE), or isolated from solvent in the gas phase, oligopeptides readily adopt stable α-helical structure. Furthermore, crosslinks can be incorporated into peptides to conformationally stabilize helical folds. Crosslinks stabilize the helical state by entropically destabilizing the unfolded state and by removing enthalpically stabilized "decoy" folds that compete with the fully helical state. It has been shown that α-helices are more stable, robust to mutations and designable than β-strands in natural proteins, and also in artificially designed proteins. 168: 199: 447: 1504:α-Helices under axial tensile deformation, a characteristic loading condition that appears in many alpha-helix-rich filaments and tissues, results in a characteristic three-phase behavior of stiff-soft-stiff tangent modulus. Phase I corresponds to the small-deformation regime during which the helix is stretched homogeneously, followed by phase II, in which alpha-helical turns break mediated by the rupture of groups of H-bonds. Phase III is typically associated with large-deformation covalent bond stretching. 392: 4413: 1597:

to the artist, "the flowers reflect the various types of sidechains that each amino acid holds out to the world". This same metaphor is also echoed from the scientist's side: "β sheets do not show a stiff repetitious regularity but flow in graceful, twisting curves, and even the α-helix is regular more in the manner of a flower stem, whose branching nodes show the influence of environment, developmental history, and the evolution of each part to match its own idiosyncratic function."

1411: 1563: 123: 604:, (2) a wenxiang diagram, and (3) a helical net. Each of these can be visualized with various software packages and web servers. To generate a small number of diagrams, Heliquest can be used for helical wheels, and NetWheels can be used for helical wheels and helical nets. To programmatically generate a large number of diagrams, helixvis can be used to draw helical wheels and wenxiang diagrams in the R and Python programming languages. 1369: 1488:), it is presumed because the helical structure can satisfy all backbone hydrogen-bonds internally, leaving no polar groups exposed to the membrane if the sidechains are hydrophobic. Proteins are sometimes anchored by a single membrane-spanning helix, sometimes by a pair, and sometimes by a helix bundle, most classically consisting of seven helices arranged up-and-down in a ring such as for 1209:, or sometimes a phosphate ion. Some regard the helix macrodipole as interacting electrostatically with such groups. Others feel that this is misleading and it is more realistic to say that the hydrogen bond potential of the free NH groups at the N-terminus of an α-helix can be satisfied by hydrogen bonding; this can also be regarded as set of interactions between local microdipoles such as 1431: 1603:

is a German-born sculptor with degrees in experimental physics and sculpture. Since 2001 Voss-Andreae creates "protein sculptures" 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

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San Francisco area artist Julie Newdoll, who holds a degree in microbiology with 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

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structure where each amino acid residue 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. Dunitz describes how Pauling's first article on the theme in fact shows a left-handed helix, the

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per residue in an α-helical configuration, relative to alanine arbitrarily set as zero. Higher numbers (more positive free energy changes) are less favoured. Significant deviations from these average numbers are possible, depending on the identities of the neighbouring residues.

1360:, and many models have been devised to describe how this relates to their function. Common to many of them is that the hydrophobic face of the antimicrobial peptide forms pores in the plasma membrane after associating with the fatty chains at the membrane core. 730:(having no amide hydrogen), and also because its sidechain interferes sterically with the backbone of the preceding turn – inside a helix, this forces a bend of about 30° in the helix's axis. However, proline is often seen as the 540:

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 "downward" (i.e., toward the N-terminus), like the branches of an evergreen tree

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such as the example shown at right. It is clear that all the backbone carbonyl oxygens point downward (toward the C-terminus) but splay out slightly, and the H-bonds are approximately parallel to the helix axis. Protein structures from

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is at the bottom and its C-terminus at the top. Note that the sidechains (black stubs) angle slightly downward, toward the N-terminus, while the peptide oxygens (red) point up and the peptide NHs (blue with grey stubs) point

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motifs. This is because of the convenient structural fact that the diameter of an α-helix is about 12 Å (1.2 nm) including an average set of sidechains, about the same as the width of the major groove in B-form

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groups of the peptide bond pointing along the helix axis. The effects of this macrodipole are a matter of some controversy. α-helices often occur with the N-terminal end bound by a negatively charged group, sometimes an

1608:, the discoverer of the α-helix, is fashioned from a large steel beam rearranged in the structure of the α-helix. The 10-foot-tall (3 m), bright-red sculpture stands in front of Pauling's childhood home in 590:

An α-helix in ultrahigh-resolution electron density contours, with oxygen atoms in red, nitrogen atoms in blue, and hydrogen bonds as green dotted lines (PDB file 2NRL, 17–32). The N-terminus is at the top,

1496:(GPCRs). The structural stability between pairs of α-Helical transmembrane domains rely on conserved membrane interhelical packing motifs, for example, the Glycine-xxx-Glycine (or small-xxx-small) motif. 379:

torsion angles (see below) and rule 6.3 in terms of the combined pattern of pitch and hydrogen bonding. The α-helices can be identified in protein structure using several computational methods, such as

347:. The pitch of the alpha-helix (the vertical distance between consecutive turns of the helix) is 5.4 Å (0.54 nm), which is the product of 1.5 and 3.6. The most important thing is that the 1472:(or leucine zipper) dimers of helices can readily position a pair of interaction surfaces to contact the sort of symmetrical repeat common in double-helical DNA. An example of both aspects is the 1634:. Byron Rubin is a former protein crystallographer now professional sculptor in metal of proteins, nucleic acids, and drug molecules – many of which featuring α-helices, such as 443:

helix, and on average, 3.6 amino acids are involved in one ring of α-helix. The subscripts refer to the number of atoms (including the hydrogen) in the closed loop formed by the hydrogen bond.

1391:, have very similar folds made up of about 70% α-helix, with the rest being non-repetitive regions, or "loops" that connect the helices. In classifying proteins by their dominant fold, the 2206:

Lovell SC, Davis IW, Arendall WB, de Bakker PI, Word JM, Prisant MG, Richardson JS, Richardson DC (February 2003). "Structure validation by Calpha geometry: phi,psi and Cbeta deviation".

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in 1951 (see below); that paper showed both right- and left-handed helices, although in 1960 the crystal structure of myoglobin showed that the right-handed form is the common one.

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because there are 3.6 amino acids in one ring, with 13 atoms being involved in the ring formed by the hydrogen bond (starting with amidic hydrogen and ending with carbonyl oxygen)

1735:, Dickerson RE, Strandberg BE, Hart RG, Davies DR, Phillips DC, Shore VC (February 1960). "Structure of myoglobin: A three-dimensional Fourier synthesis at 2 Å resolution". 1520:

and analyzed via the quasi-continuum model. Helices not stabilized by tertiary interactions show dynamic behavior, which can be mainly attributed to helix fraying from the ends.

1313:, 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. 371:

hydrogen bonding is the most prominent characteristic of an α-helix. Official international nomenclature specifies two ways of defining α-helices, rule 6.2 in terms of repeating

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of moist wool or hair fibers upon significant stretching. The data suggested that the unstretched fibers had a coiled molecular structure with a characteristic repeat of ≈5.1

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Max (see image at left), which uses a helical coiled coil to dimerize, positioning another pair of helices for interaction in two successive turns of the DNA major groove.

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Since the α-helix is defined by its hydrogen bonds and backbone conformation, the most detailed experimental evidence for α-helical structure comes from atomic-resolution

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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). In general, short

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plot), with data points for α-helical residues forming a dense diagonal cluster below and left of center, around the global energy minimum for backbone conformation.

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also tends to disrupt helices because its high conformational flexibility makes it entropically expensive to adopt the relatively constrained α-helical structure.

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Kohn, Eric M.; Shirley, David J.; Arotsky, Lubov; Picciano, Angela M.; Ridgway, Zachary; Urban, Michael W.; Carone, Benjamin R.; Caputo, Gregory A. (2018-02-04).

625:(NOE) couplings between atoms on adjacent helical turns. In some cases, the individual hydrogen bonds can be observed directly as a small scalar coupling in NMR. 3914:

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

1265:, which is a type of coiled-coil. These hydrophobic residues pack together in the interior of the helix bundle. In general, the fifth and seventh residues (the 280:

was the first to show that Astbury's models could not be correct in detail, because they involved clashes of atoms. Neurath's paper and Astbury's data inspired

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cost associated with the folding of the polypeptide chain is not compensated for by a sufficient amount of stabilizing interactions. In general, the backbone

4191: 3881:"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" 116: 4150: 545:

effect). This directionality is sometimes used in preliminary, low-resolution electron-density maps to determine the direction of the protein backbone.

53:. It is also the most extreme type of local structure, and it is the local structure that is most easily predicted from a sequence of amino acids. 2110:

Kabsch W, Sander C (December 1983). "Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features".

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is now capable of discerning individual α-helices within a protein, although their assignment to residues is still an active area of research.

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detail. Two hydrogen bonds for the same peptide group are highlighted in magenta; the H to O distance is about 2 Å (0.20 nm). The

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Long homopolymers of amino acids often form helices if soluble. Such long, isolated helices can also be detected by other methods, such as

3018:"Dominant role of local dipoles in stabilizing uncompensated charges on a sulfate sequestered in a periplasmic active transport protein" 3846:"X-ray studies of the structures of hair, wool and related fibres. II. The molecular structure and elastic properties of hair keratin" 2628: 4184: 3275:"Hierarchies, multiple energy barriers, and robustness govern the fracture mechanics of alpha-helical and beta-sheet protein domains" 2756:

Mol AR, Castro MS, Fontes W (2018). "NetWheels: A web application to create high quality peptide helical wheel and net projections".

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Astbury initially proposed a linked-chain structure for the fibers. He later joined other researchers (notably the American chemist

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Although incorrect in their details, Astbury's models of these forms were correct in essence and correspond to modern elements of

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Coiled-coil α helices are highly stable forms in which two or more helices wrap around each other in a "supercoil" structure.

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Hudgins RR, Jarrold MF (1999). "Helix Formation in Unsolvated Alanine-Based Peptides: Helical Monomers and Helical Dimers".

4177: 493:(of slope −1), ranging from (−90°, −15°) to (−70°, −35°). For comparison, the sum of the dihedral angles for a 3 477:

around (−60°, −45°), as shown in the image at right. In more general terms, they adopt dihedral angles such that the

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residue sum to roughly −105°. As a consequence, α-helical dihedral angles, in general, fall on a diagonal stripe on the

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Changes in binding orientation also occur for facially-organized oligopeptides. This pattern is especially common in

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Astbury WT (1933). "Some Problems in the X-ray Analysis of the Structure of Animal Hairs and Other Protein Fibers".

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of α-helices are a prominent element in the laser-etched crystal sculptures of protein structures created by artist

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enantiomer of the true structure. Short pieces of left-handed helix sometimes occur with a large content of achiral

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method, characterized by two parameters: the propensity to initiate a helix and the propensity to extend a helix.

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spectrum of helices is also idiosyncratic, exhibiting a pronounced double minimum at around 208 and 222 nm.

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The 3 most popular ways of visualizing the alpha-helical secondary structure of oligopeptide sequences are (1) a

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helix is roughly −75°, whereas that for the π-helix is roughly −130°. The general formula for the rotation angle

3234:"De novo design of transmembrane helix–helix interactions and measurement of stability in a biological membrane" 2560:"Use of helical wheels to represent the structures of proteins and to identify segments with helical potential" 1585:

At least five artists have made explicit reference to the α-helix in their work: Julie Newdoll in painting and

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file 1GZM), with a bundle of seven helices crossing the membrane (membrane surfaces marked by horizontal lines)

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groups are pointing upwards toward the viewer, spaced roughly 100° apart on the circle, corresponding to 3.6

117: 3424:"Biological functions of low-frequency vibrations (phonons). III. Helical structures and microenvironment" 2836:

Subramanian V, Wadhwa RR, Stevens-Truss R (2020). "Helixvis: Visualize alpha-helical peptides in Python".

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Two key developments in the modeling of the modern α-helix were: the correct bond geometry, thanks to the

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Chou KC, Zhang CT, Maggiora GM (1997). "Disposition of amphiphilic helices in heteropolar environments".

1543: 1325:, a representation that illustrates the orientations of the constituent amino acids (see the article for 652: 137: 46: 4437: 2965:

Hol WG, van Duijnen PT, Berendsen HJ (1978). "The alpha helix dipole and the properties of proteins".

4486: 636: 622: 1698: 1657:. Tyka has been making sculptures of protein molecules since 2010 from copper and steel, including 1654: 1650: 1538:) can adopt α-helical structure at low temperature that is "melted out" at high temperatures. This 1301: – is a very common structural motif in proteins. For example, it occurs in human 252:

the stretching caused the helix to uncoil, forming an extended state (which he called the β-form).

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Murzin AG, Finkelstein AV (December 1988). "General architecture of the alpha-helical globule".

3700:"The discovery of the alpha-helix and beta-sheet, the principal structural features of proteins" 2395:"All-atom model for stabilization of alpha-helical structure in peptides by hydrocarbon staples" 1943:"The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain" 1484:α-Helices are also the most common protein structure element that crosses biological membranes ( 2000: 1876: 1415: 1357: 289: 80: 586: 4604: 4402: 4344: 2269: 1846: 1547: 1485: 663: 613: 285: 242: 2503:"Global analysis of protein folding using massively parallel design, synthesis, and testing" 1573:(2004), powder coated steel, height 10 ft (3 m). The sculpture stands in front of 690:

Different amino-acid sequences have different propensities for forming α-helical structure.

4553: 3973: 3892: 3857: 3801: 3760: 3711: 3492: 3435: 3286: 2974: 2921: 2864: 2800: 2671: 2571: 2514: 2455: 2322: 2273: 1954: 1896: 1744: 1712: 1639: 1473: 1399: 1346: 788: 490: 439: + 4 spacing adds three more atoms to the H-bonded loop compared to the tighter 3 1239:

residues, not DNA base-pairs). The first and especially the fourth residues (known as the

8: 4614: 4271: 2054:"Abbreviations and symbols for the description of the conformation of polypeptide chains" 1789:(1940). "Intramolecular folding of polypeptide chains in relation to protein structure". 1693: 1600: 1586: 1566: 734:

residue of a helix, it is presumed due to its structural rigidity. At the other extreme,

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Chothia C, Levitt M, Richardson D (January 1981). "Helix to helix packing in proteins".

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There are several lower-resolution methods for assigning general helical structure. The

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NetSurfP ver. 1.1 – Protein Surface Accessibility and Secondary Structure Predictions

4123: 4119: 4094: 4090: 4065: 4060: 4043: 4030: 4026: 4001: 3948: 3739: 3683: 3520: 3461: 3404: 3355: 3314: 3255: 3196: 3188: 3147: 3096: 3047: 2990: 2947: 2890: 2738: 2697: 2632: 2597: 2540: 2483: 2424: 2348: 2289: 2277: 2223: 2188: 2178: 2127: 2034: 1982: 1816: 1760: 1662: 1435: 1423: 1337:, an α-helix will exhibit two "faces" – one containing predominantly 747: 576: 450: 281: 227: 142: 3935: 3586: 3541: 2822: 2773: 2733: 2717:"HELIQUEST: a web server to screen sequences with specific alpha-helical properties" 2716: 2644: 2139: 1916: 4650: 4447: 4337: 4314: 4115: 4086: 4055: 4022: 3991: 3981: 3923: 3900: 3865: 3832: 3809: 3780: 3768: 3729: 3719: 3574: 3510: 3500: 3451: 3443: 3394: 3386: 3345: 3304: 3294: 3245: 3178: 3137: 3127: 3086: 3078: 3037: 3029: 3002: 2982: 2937: 2929: 2880: 2872: 2808: 2761: 2728: 2687: 2679: 2624: 2587: 2579: 2530: 2522: 2473: 2463: 2414: 2406: 2375: 2338: 2330: 2235: 2215: 2170: 2119: 2085: 2065: 2026: 1972: 1962: 1904: 1858: 1798: 1772: 1752: 1643: 1609: 1578: 1452: 1342: 1330: 1256: 675: 580: 381: 167: 3481:"Local conformational dynamics in alpha-helices measured by fast triplet transfer" 3167:"Antimicrobial peptides: new candidates in the fight against bacterial infections" 198: 4580: 4432: 4382: 4154: 3565:

Voss-Andreae J (2005). "Protein Sculptures: Life's Building Blocks Inspire Art".

3250: 3233: 2910:"A Helix Propensity Scale Based on Experimental Studies of Peptides and Proteins" 2853:"A helix propensity scale based on experimental studies of peptides and proteins" 2468: 1688: 1615: 1551: 1388: 1278: 554: 446: 300: 220: 2051: 4511: 4397: 4250: 3966: