Abstract
The possibilities of packing α-helices are limited. The α-helices of a protein must be arranged so that the closely packed side-chains do not clash sterically and that their chemical properties are compatible. The packing of α-helices of closely related proteins can be very similar; however, slight variations and the presence of different amino acids can lead to different properties and functions. First, we will investigate the structure of three DNA-binding proteins that have α-helices in an arrangement known as a coiled coil. Variation in the amino acid sequence in the regions forming the coiled coils determines whether the proteins can form homodimers or heterodimers. Then, we will examine the arrangement of the α-helices in the globular protein myoglobin. In the final part of the chapter, we move on to investigate the variations in the structure and functions of three proteins. All three proteins have similar α-helical Bcl-2-like folds but perform different functions. One protein acts to prevent the onset of apoptosis (i.e., it is a pro-survival factor for a cell), whereas the second acts to induce the onset of apoptosis (i.e., it is a pro-apoptotic factor). The third, from vaccinia virus, does not show any apoptotic properties but can instead inhibit cellular signaling pathways to prevent inflammation in the infected host (◘ Table 7.1).
Variety is the very spice of life, that gives it all its flavor. William Cowper
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References
Adams JM, Cory S (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281(5381):1322–1326
Adhikary S, Eilers M (2005) Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 6(8):635–645. https://doi.org/10.1038/nrm1703
Blankenfeldt W, Thoma NH, Wray JS, Gautel M, Schlichting I (2006) Crystal structures of human cardiac beta-myosin II S2-Delta provide insight into the functional role of the S2 subfragment. Proc Natl Acad Sci U S A 103(47):17713–17717. https://doi.org/10.1073/pnas.0606741103
Chothia C, Levitt M, Richardson D (1977) Structure of proteins: packing of alpha-helices and pleated sheets. Proc Natl Acad Sci U S A 74(10):4130–4134
Crick FH (1952) Is alpha-keratin a coiled coil? Nature 170(4334):882–883
Crick FHC (1953) The packing of alpha-helices - simple coiled-coils. Acta Crystallogr 6(8-9):689–697. https://doi.org/10.1107/S0365110x53001964
Ellenberger TE, Brandl CJ, Struhl K, Harrison SC (1992) The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted alpha helices: crystal structure of the protein-DNA complex. Cell 71(7):1223–1237
Fedosyuk S, Bezerra GA, Radakovics K, Smith TK, Sammito M, Bobik N, Round A, Ten Eyck LF, Djinovic-Carugo K, Uson I, Skern T (2016) Vaccinia virus Immunomodulator A46: a lipid and protein-binding scaffold for sequestering host TIR-domain proteins. PLoS Pathog 12(12):e1006079. https://doi.org/10.1371/journal.ppat.1006079
Fedosyuk S, Grishkovskaya I, de Almeida Ribeiro E Jr, Skern T (2014) Characterization and structure of the vaccinia virus NF-kappaB antagonist A46. J Biol Chem 289(6):3749–3762. https://doi.org/10.1074/jbc.M113.512756
Ferre-D'Amare AR, Prendergast GC, Ziff EB, Burley SK (1993) Recognition by max of its cognate DNA through a dimeric b/HLH/Z domain. Nature 363(6424):38–45. https://doi.org/10.1038/363038a0
Franklin E, Khan AR (2013) Poxvirus antagonism of innate immunity by Bcl-2 fold proteins. J Struct Biol 181(1):1–10. https://doi.org/10.1016/j.jsb.2012.10.015
Gamblin SJ, Haire LF, Russell RJ, Stevens DJ, Xiao B, Ha Y, Vasisht N, Steinhauer DA, Daniels RS, Elliot A, Wiley DC, Skehel JJ (2004) The structure and receptor binding properties of the 1918 influenza hemagglutinin. Science 303(5665):1838–1842. https://doi.org/10.1126/science.1093155
Graham SC, Bahar MW, Cooray S, Chen RA, Whalen DM, Abrescia NG, Alderton D, Owens RJ, Stuart DI, Smith GL, Grimes JM (2008) Vaccinia virus proteins A52 and B14 share a Bcl-2-like fold but have evolved to inhibit NF-kappaB rather than apoptosis. PLoS Pathog 4(8):e1000128. https://doi.org/10.1371/journal.ppat.1000128
Grinberg AV, Hu CD, Kerppola TK (2004) Visualization of Myc/Max/Mad family dimers and the competition for dimerization in living cells. Mol Cell Biol 24(10):4294–4308
Ku B, Liang C, Jung JU, Oh BH (2011) Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX. Cell Res 21(4):627–641. https://doi.org/10.1038/cr.2010.149
Kvansakul M, Caria S, Hinds MG (2017) The Bcl-2 family in host-virus interactions. Virus 9(10). https://doi.org/10.3390/v9100290
Kvansakul M, Yang H, Fairlie WD, Czabotar PE, Fischer SF, Perugini MA, Huang DC, Colman PM (2008) Vaccinia virus anti-apoptotic F1L is a novel Bcl-2-like domain-swapped dimer that binds a highly selective subset of BH3-containing death ligands. Cell Death Differ 15(10):1564–1571. https://doi.org/10.1038/cdd.2008.83
Landschulz WH, Johnson PF, McKnight SL (1988) The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science 240(4860):1759–1764
Luna-Vargas MP, Chipuk JE (2016) The deadly landscape of pro-apoptotic BCL-2 proteins in the outer mitochondrial membrane. FEBS J 283(14):2676–2689. https://doi.org/10.1111/febs.13624
Lysakova-Devine T, Keogh B, Harrington B, Nagpal K, Halle A, Golenbock DT, Monie T, Bowie AG (2010) Viral inhibitory peptide of TLR4, a peptide derived from vaccinia protein A46, specifically inhibits TLR4 by directly targeting MyD88 adaptor-like and TRIF-related adaptor molecule. J Immunol 185(7):4261–4271. https://doi.org/10.4049/jimmunol.1002013
Ma PC, Rould MA, Weintraub H, Pabo CO (1994) Crystal structure of MyoD bHLH domain-DNA complex: perspectives on DNA recognition and implications for transcriptional activation. Cell 77(3):451–459
Mason JM, Arndt KM (2004) Coiled coil domains: stability, specificity, and biological implications. Chembiochem 5(2):170–176. https://doi.org/10.1002/cbic.200300781
Nair SK, Burley SK (2003) X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors. Cell 112(2):193–205
Nobbs CL, Watson HC, Kendrew JC (1966) Structure of deoxymyoglobin: a crystallographic study. Nature 209(5021):339–341
O’Shea EK, Klemm JD, Kim PS, Alber T (1991) X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil. Science 254(5031):539–544
Pauling L, Corey RB (1953) Compound helical configurations of polypeptide chains: structure of proteins of the alpha-keratin type. Nature 171(4341):59–61
Pauling L, Corey RB, Branson HR (1951) The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. Proc Natl Acad Sci U S A 37(4):205–211
Perutz MF (1951) New X-ray evidence on the configuration of polypeptide chains. Nature 167(4261):1053–1054
Petros AM, Medek A, Nettesheim DG, Kim DH, Yoon HS, Swift K, Matayoshi ED, Oltersdorf T, Fesik SW (2001) Solution structure of the antiapoptotic protein bcl-2. Proc Natl Acad Sci U S A 98(6):3012–3017. https://doi.org/10.1073/pnas.041619798
Rech de Laval V, Deleage G, Aouacheria A, Combet C (2014) BCL2DB: database of BCL-2 family members and BH3-only proteins. Database (Oxford) 2014:bau013. https://doi.org/10.1093/database/bau013
Sodek J, Hodges RS, Smillie LB, Jurasek L (1972) Amino-acid sequence of rabbit skeletal tropomyosin and its coiled-coil structure. Proc Natl Acad Sci U S A 69(12):3800–3804
Suzuki M, Youle RJ, Tjandra N (2000) Structure of Bax: coregulation of dimer formation and intracellular localization. Cell 103(4):645–654
Truebestein L, Leonard TA (2016) Coiled-coils: the long and short of it. BioEssays 38(9):903–916. https://doi.org/10.1002/bies.201600062
Wallis M (2014) Molecular evolution of growth hormone. The Biochemist, vol 36. Biochemical Society, London
Wilson IA, Skehel JJ, Wiley DC (1981) Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 a resolution. Nature 289(5796):366–373
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Skern, T. (2018). Examining α-Helical Proteins. In: Exploring Protein Structure: Principles and Practice. Learning Materials in Biosciences. Springer, Cham. https://doi.org/10.1007/978-3-319-76858-8_7
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