Alpha helix
An alpha helix (or
The alpha helix is the most common structural arrangement in the secondary structure of proteins. 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.
The alpha helix has a right-handed helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid that is four residues earlier in the protein sequence.
Other names
[edit]The alpha helix is also commonly called a:
- Pauling–Corey–Branson
α -helix (from the names of three scientists who described its structure) - 3.613-helix 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)
Discovery
[edit]In the early 1930s, William Astbury showed that there were drastic changes in the X-ray fiber diffraction 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 ångströms (0.51 nanometres).
Astbury initially proposed a linked-chain structure for the fibers. He later joined other researchers (notably the American chemist Maurice Huggins) in proposing that:
- the unstretched protein molecules formed a helix (which he called the
α -form) - the stretching caused the helix to uncoil, forming an extended state (which he called the
β -form).
Although incorrect in their details, Astbury's models of these forms were correct in essence and correspond to modern elements of secondary structure, the
Two key developments in the modeling of the modern
Structure
[edit]Geometry and hydrogen bonding
[edit]The amino acids in an
Similar structures include the 310 helix (i + 3 → i hydrogen bonding) and the
Residues in
- 3 cos
Ω = 1 − 4 cos2 φ +ψ /2
The
Stability
[edit]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 polypeptides do not exhibit much
Visualization
[edit]The 3 most popular ways of visualizing the alpha-helical secondary structure of oligopeptide sequences are (1) a helical wheel,[21] (2) a wenxiang diagram,[22] and (3) a helical net.[23] Each of these can be visualized with various software packages and web servers. To generate a small number of diagrams, Heliquest[24] can be used for helical wheels, and NetWheels[25] can be used for helical wheels and helical nets. To programmatically generate a large number of diagrams, helixvis[26][27] can be used to draw helical wheels and wenxiang diagrams in the R and Python programming languages.
Experimental determination
[edit]Since the
There are several lower-resolution methods for assigning general helical structure. The NMR chemical shifts (in particular of the C
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 the diffusion constant. In stricter terms, these methods detect only the characteristic prolate (long cigar-like) hydrodynamic shape of a helix, or its large dipole moment.
Amino-acid propensities
[edit]Different amino-acid sequences have different propensities for forming
Table of standard amino acid alpha-helical propensities
[edit]Estimated differences in free energy change,
Differences in free energy change per residue[29] Amino acid 3-
letter1-
letterHelical penalty kcal/mol kJ/mol Alanine Ala A 0.00 0.00 Arginine Arg R 0.21 0.88 Asparagine Asn N 0.65 2.72 Aspartic acid Asp D 0.69 2.89 Cysteine Cys C 0.68 2.85 Glutamic acid Glu E 0.40 1.67 Glutamine Gln Q 0.39 1.63 Glycine Gly G 1.00 4.18 Histidine His H 0.61 2.55 Isoleucine Ile I 0.41 1.72 Leucine Leu L 0.21 0.88 Lysine Lys K 0.26 1.09 Methionine Met M 0.24 1.00 Phenylalanine Phe F 0.54 2.26 Proline Pro P 3.16 13.22 Serine Ser S 0.50 2.09 Threonine Thr T 0.66 2.76 Tryptophan Trp W 0.49 2.05 Tyrosine Tyr Y 0.53 2.22 Valine Val V 0.61 2.55
Dipole moment
[edit]A helix has an overall dipole moment due to the aggregate effect of the individual microdipoles from the carbonyl groups of the peptide bond pointing along the helix axis.[30] The effects of this macrodipole are a matter of some controversy.
Coiled coils
[edit]Coiled-coil
Facial arrangements
[edit]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 (see the article for leucine zipper for such a diagram). Often in globular proteins, as well as in specialized structures such as coiled-coils and leucine zippers, an
Changes in binding orientation also occur for facially-organized oligopeptides. This pattern is especially common in antimicrobial peptides, 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.[33][34]
Larger-scale assemblies
[edit]Myoglobin and hemoglobin, the first two proteins whose structures were solved by X-ray crystallography, have very similar folds made up of about 70%
Hemoglobin then has an even larger-scale quaternary structure, in which the functional oxygen-binding molecule is made up of four subunits.
Functional roles
[edit]DNA binding
[edit]Membrane spanning
[edit]Mechanical properties
[edit]Dynamical features
[edit]Alpha-helices in proteins may have low-frequency accordion-like motion as observed by the Raman spectroscopy[39] and analyzed via the quasi-continuum model.[40][41] Helices not stabilized by tertiary interactions show dynamic behavior, which can be mainly attributed to helix fraying from the ends.[42]
Helix–coil transition
[edit]Homopolymers of amino acids (such as polylysine) can adopt
In art
[edit]At least five artists have made explicit reference to the
San Francisco area artist Julie Newdoll,[43] 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
Julian Voss-Andreae is a German-born sculptor with degrees in experimental physics and sculpture. Since 2001 Voss-Andreae creates "protein sculptures"[44] based on protein structure with the
Ribbon diagrams of
Mike Tyka is a computational biochemist at the University of Washington working with David Baker. Tyka has been making sculptures of protein molecules since 2010 from copper and steel, including ubiquitin and a potassium channel tetramer.[47]
See also
[edit]- 310 helix
- Beta sheet
- Davydov soliton
- Folding (chemistry)
- Knobs into holes packing
- Pi helix
- Proteopedia Helices_in_Proteins
References
[edit]- ^ Kendrew JC, 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". Nature. 185 (4711): 422–7. Bibcode:1960Natur.185..422K. doi:10.1038/185422a0. PMID 18990802. S2CID 4167651.
- ^ Neurath H (1940). "Intramolecular folding of polypeptide chains in relation to protein structure". Journal of Physical Chemistry. 44 (3): 296–305. doi:10.1021/j150399a003.
- ^ Taylor HS (1942). "Large molecules through atomic spectacles". Proceedings of the American Philosophical Society. 85 (1): 1–12. JSTOR 985121.
- ^ Huggins M (1943). "The structure of fibrous proteins". Chemical Reviews. 32 (2): 195–218. doi:10.1021/cr60102a002.
- ^ Bragg WL, Kendrew JC, Perutz MF (1950). "Polypeptide chain configurations in crystalline proteins". Proceedings of the Royal Society of London, Series A. 203 (1074): 321–?. Bibcode:1950RSPSA.203..321B. doi:10.1098/rspa.1950.0142. S2CID 93804323.
- ^ Pauling L, Corey RB, Branson HR (April 1951). "The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain". Proceedings of the National Academy of Sciences of the United States of America. 37 (4): 205–11. Bibcode:1951PNAS...37..205P. doi:10.1073/pnas.37.4.205. PMC 1063337. PMID 14816373.
- ^ "The Nobel Prize in Chemistry 1954".
- ^ Dunitz J (2001). "Pauling's Left-Handed
α -Helix". Angewandte Chemie International Edition. 40 (22): 4167–4173. doi:10.1002/1521-3773(20011119)40:22<4167::AID-ANIE4167>3.0.CO;2-Q. PMID 29712120. - ^ IUPAC-IUB Commission on Biochemical Nomenclature (1970). "Abbreviations and symbols for the description of the conformation of polypeptide chains". Journal of Biological Chemistry. 245 (24): 6489–6497. doi:10.1016/S0021-9258(18)62561-X.
- ^ "Polypeptide Conformations 1 and 2". www.sbcs.qmul.ac.uk. Retrieved 5 November 2018.
- ^ Kabsch W, Sander C (December 1983). "Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features". Biopolymers. 22 (12): 2577–637. doi:10.1002/bip.360221211. PMID 6667333. S2CID 29185760.
- ^ a b c Richardson JS (1981). "The anatomy and taxonomy of protein structure". Advances in Protein Chemistry. 34: 167–339. doi:10.1016/S0065-3233(08)60520-3. ISBN 9780120342341. PMID 7020376.
- ^ 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". Proteins. 50 (3): 437–50. doi:10.1002/prot.10286. PMID 12557186. S2CID 8358424.
- ^ Dickerson RE, Geis I (1969), Structure and Action of Proteins, Harper, New York
- ^ Zorko, Matjaž (2010). "Structural Organization of Proteins". In Langel, Ülo; Cravatt, Benjamin F.; Gräslund, Astrid; von Heijne, Gunnar; Land, Tiit; Niessen, Sherry; Zorko, Matjaž (eds.). Introduction to Peptides and Proteins. Boca Raton: CRC Press. pp. 36–57. ISBN 9781439882047.
- ^ Terwilliger TC (March 2010). "Rapid model building of alpha-helices in electron-density maps". Acta Crystallographica Section D. 66 (Pt 3): 268–75. Bibcode:2010AcCrD..66..268T. doi:10.1107/S0907444910000314. PMC 2827347. PMID 20179338.
- ^ Hudgins RR, Jarrold MF (1999). "Helix Formation in Unsolvated Alanine-Based Peptides: Helical Monomers and Helical Dimers". Journal of the American Chemical Society. 121 (14): 3494–3501. doi:10.1021/ja983996a.
- ^ Kutchukian PS, Yang JS, Verdine GL, Shakhnovich EI (April 2009). "All-atom model for stabilization of alpha-helical structure in peptides by hydrocarbon staples". Journal of the American Chemical Society. 131 (13): 4622–7. doi:10.1021/ja805037p. PMC 2735086. PMID 19334772.
- ^ Abrusan G, Marsh JA (2016). "Alpha helices are more robust to mutations than beta strands". PLOS Computational Biology. 12 (12): e1005242. Bibcode:2016PLSCB..12E5242A. doi:10.1371/journal.pcbi.1005242. PMC 5147804. PMID 27935949.
- ^ Rocklin GJ, et al. (2017). "Global analysis of protein folding using massively parallel design, synthesis, and testing". Science. 357 (6347): 168–175. Bibcode:2017Sci...357..168R. doi:10.1126/science.aan0693. PMC 5568797. PMID 28706065.
- ^ Schiffer M, Edmundson AB (1967). "Use of helical wheels to represent the structures of proteins and to identify segments with helical potential". Biophysical Journal. 7 (2): 121–135. Bibcode:1967BpJ.....7..121S. doi:10.1016/S0006-3495(67)86579-2. PMC 1368002. PMID 6048867.
- ^ Chou KC, Zhang CT, Maggiora GM (1997). "Disposition of amphiphilic helices in heteropolar environments". Proteins: Structure, Function, and Genetics. 28 (1): 99–108. doi:10.1002/(SICI)1097-0134(199705)28:1<99::AID-PROT10>3.0.CO;2-C. PMID 9144795. S2CID 26944184.
- ^ Dunnill P (1968). "The Use of Helical Net-Diagrams to Represent Protein Structures". Biophysical Journal. 8 (7): 865–875. Bibcode:1968BpJ.....8..865D. doi:10.1016/S0006-3495(68)86525-7. PMC 1367563. PMID 5699810.
- ^ Gautier R, Douguet D, Antonny B, Drin G (2008). "HELIQUEST: a web server to screen sequences with specific alpha-helical properties". Bioinformatics. 24 (18): 2101–2102. doi:10.1093/bioinformatics/btn392. PMID 18662927.
- ^ Mol AR, Castro MS, Fontes W (2018). "NetWheels: A web application to create high quality peptide helical wheel and net projections". bioRxiv. doi:10.1101/416347. S2CID 92137153.
- ^ Wadhwa RR, Subramanian V, Stevens-Truss R (2018). "Visualizing alpha-helical peptides in R with helixvis". Journal of Open Source Software. 3 (31): 1008. Bibcode:2018JOSS....3.1008W. doi:10.21105/joss.01008. S2CID 56486576.
- ^ Subramanian V, Wadhwa RR, Stevens-Truss R (2020). "Helixvis: Visualize alpha-helical peptides in Python". ChemRxiv.
- ^ Pace CN, Scholtz JM (July 1998). "A helix propensity scale based on experimental studies of peptides and proteins". Biophysical Journal. 75 (1): 422–7. Bibcode:1998BpJ....75..422N. doi:10.1016/S0006-3495(98)77529-0. PMC 1299714. PMID 9649402.
- ^ Pace, C. Nick; Scholtz, J. Martin (1998). "A Helix Propensity Scale Based on Experimental Studies of Peptides and Proteins". Biophysical Journal. 75 (1): 422–427. Bibcode:1998BpJ....75..422N. doi:10.1016/s0006-3495(98)77529-0. PMC 1299714. PMID 9649402.
- ^ Hol WG, van Duijnen PT, Berendsen HJ (1978). "The alpha helix dipole and the properties of proteins". Nature. 273 (5662): 443–446. Bibcode:1978Natur.273..443H. doi:10.1038/273443a0. PMID 661956. S2CID 4147335.
- ^ He JJ, Quiocho FA (October 1993). "Dominant role of local dipoles in stabilizing uncompensated charges on a sulfate sequestered in a periplasmic active transport protein". Protein Science. 2 (10): 1643–7. doi:10.1002/pro.5560021010. PMC 2142251. PMID 8251939.
- ^ Milner-White EJ (November 1997). "The partial charge of the nitrogen atom in peptide bonds". Protein Science. 6 (11): 2477–82. doi:10.1002/pro.5560061125. PMC 2143592. PMID 9385654.
- ^ 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). "Role of Cationic Side Chains in the Antimicrobial Activity of C18G". Molecules. 23 (2): 329. doi:10.3390/molecules23020329. PMC 6017431. PMID 29401708.
- ^ Toke, Orsolya (2005). "Antimicrobial peptides: new candidates in the fight against bacterial infections". Biopolymers. 80 (6): 717–735. doi:10.1002/bip.20286. ISSN 0006-3525. PMID 15880793.
- ^ Branden & Tooze, chapter 10
- ^ Branden & Tooze, chapter 12.
- ^ Nash A, Notman R, Dixon AM (2015). "De novo design of transmembrane helix–helix interactions and measurement of stability in a biological membrane". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1848 (5): 1248–57. doi:10.1016/j.bbamem.2015.02.020. PMID 25732028.
- ^ Ackbarow T, Chen X, Keten S, Buehler MJ (October 2007). "Hierarchies, multiple energy barriers, and robustness govern the fracture mechanics of alpha-helical and beta-sheet protein domains". Proceedings of the National Academy of Sciences of the United States of America. 104 (42): 16410–5. Bibcode:2007PNAS..10416410A. doi:10.1073/pnas.0705759104. PMC 2034213. PMID 17925444.
- ^ Painter PC, Mosher LE, Rhoads C (July 1982). "Low-frequency modes in the Raman spectra of proteins". Biopolymers. 21 (7): 1469–72. doi:10.1002/bip.360210715. PMID 7115900.
- ^ Chou KC (December 1983). "Identification of low-frequency modes in protein molecules". The Biochemical Journal. 215 (3): 465–9. doi:10.1042/bj2150465. PMC 1152424. PMID 6362659.
- ^ Chou KC (May 1984). "Biological functions of low-frequency vibrations (phonons). III. Helical structures and microenvironment". Biophysical Journal. 45 (5): 881–9. Bibcode:1984BpJ....45..881C. doi:10.1016/S0006-3495(84)84234-4. PMC 1434967. PMID 6428481.
- ^ Fierz B, Reiner A, Kiefhaber T (January 2009). "Local conformational dynamics in alpha-helices measured by fast triplet transfer". Proceedings of the National Academy of Sciences of the United States of America. 106 (4): 1057–62. Bibcode:2009PNAS..106.1057F. doi:10.1073/pnas.0808581106. PMC 2633579. PMID 19131517.
- ^ a b "Julie Newdoll Scientifically Inspired Art, Music, Board Games". www.brushwithscience.com. Retrieved 2016-04-06.
- ^ Voss-Andreae J (2005). "Protein Sculptures: Life's Building Blocks Inspire Art". Leonardo. 38: 41–45. doi:10.1162/leon.2005.38.1.41. S2CID 57558522.
- ^ Grossman, Bathsheba. "About the Artist". Bathsheba Sculpture. Retrieved 2016-04-06.
- ^ "About". molecularsculpture.com. Retrieved 2016-04-06.
- ^ Tyka, Mike. "About". www.miketyka.com. Retrieved 2016-04-06.
Further reading
[edit]- Tooze J, Brändén CI (1999). Introduction to protein structure. New York: Garland Pub. ISBN 0-8153-2304-2..
- Eisenberg D (September 2003). "The discovery of the alpha-helix and beta-sheet, the principal structural features of proteins". Proceedings of the National Academy of Sciences of the United States of America. 100 (20): 11207–10. Bibcode:2003PNAS..10011207E. doi:10.1073/pnas.2034522100. PMC 208735. PMID 12966187.
- Astbury WT, Woods HJ (1931). "The Molecular Weights of Proteins". Nature. 127 (3209): 663–665. Bibcode:1931Natur.127..663A. doi:10.1038/127663b0. S2CID 4133226.
- Astbury WT, Street A (1931). "X-ray studies of the structures of hair, wool and related fibres. I. General". Philosophical Transactions of the Royal Society of London, Series A. 230: 75–101. Bibcode:1932RSPTA.230...75A. doi:10.1098/rsta.1932.0003.
- Astbury WT (1933). "Some Problems in the X-ray Analysis of the Structure of Animal Hairs and Other Protein Fibers". Trans. Faraday Soc. 29 (140): 193–211. doi:10.1039/tf9332900193.
- Astbury WT, 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". Philosophical Transactions of the Royal Society of London, Series A. 232 (707–720): 333–394. Bibcode:1934RSPTA.232..333A. doi:10.1098/rsta.1934.0010.
- Astbury WT, 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". Proceedings of the Royal Society of London, Series A. 150 (871): 533–551. Bibcode:1935RSPSA.150..533A. doi:10.1098/rspa.1935.0121.
- Sugeta H, Miyazawa T (1967). "General Method for Calculating Helical Parameters of Polymer Chains from Bond Lengths, Bond Angles, and Internal-Rotation Angles". Biopolymers. 5 (7): 673–679. doi:10.1002/bip.1967.360050708. S2CID 97785907.
- Wada A (1976). "The alpha-helix as an electric macro-dipole". Advances in Biophysics: 1–63. PMID 797240.
- Chothia C, Levitt M, Richardson D (October 1977). "Structure of proteins: packing of alpha-helices and pleated sheets". Proceedings of the National Academy of Sciences of the United States of America. 74 (10): 4130–4. Bibcode:1977PNAS...74.4130C. doi:10.1073/pnas.74.10.4130. PMC 431889. PMID 270659.
- Chothia C, Levitt M, Richardson D (January 1981). "Helix to helix packing in proteins". Journal of Molecular Biology. 145 (1): 215–50. doi:10.1016/0022-2836(81)90341-7. PMID 7265198.
- Hol WG (1985). "The role of the alpha-helix dipole in protein function and structure". Progress in Biophysics and Molecular Biology. 45 (3): 149–95. doi:10.1016/0079-6107(85)90001-X. PMID 3892583.
- Barlow DJ, Thornton JM (June 1988). "Helix geometry in proteins". Journal of Molecular Biology. 201 (3): 601–19. doi:10.1016/0022-2836(88)90641-9. PMID 3418712.
- Murzin AG, Finkelstein AV (December 1988). "General architecture of the alpha-helical globule". Journal of Molecular Biology. 204 (3): 749–69. doi:10.1016/0022-2836(88)90366-X. PMID 3225849.