Structural diversity in the atomic resolution 3D fingerprint of the titin M-band segment

1. Gautel M. The sarcomeric cytoskeleton: Who picks up the strain? Curr Opin Cell Biol. 2011;23: 39–46. doi: 10.1016/j.ceb.2010.12.001 21190822

2. Kontrogianni-Konstantopoulos A, Ackermann MA, Bowman AL, Yap S V, Bloch RJ. Muscle giants: Molecular Scaffolds in Sarcomerogenesis. Physiol Rev. 2009;89: 1217–67. doi: 10.1152/physrev.00017.2009 19789381

3. Gautel M, Djinović-Carugo K. The sarcomeric cytoskeleton: from molecules to motion. J Exp Biol. 2016;219: 135–45. doi: 10.1242/jeb.124941 26792323

4. Labeit S, Kolmerer B, Linke WA. The giant protein titin: Emerging roles in physiology and pathophysiology [Internet]. Circulation Research. 1997. pp. 290–294. doi: 10.1161/01.res.80.2.290 9012751

5. Tskhovrebova L, Trinick J. Titin: properties and family relationships. Nat Rev Mol Cell Biol. 2003;4: 679–689. doi: 10.1038/nrm1198 14506471

6. Mayans O, Van Der Ven PFM, Wilm M, Mues A, Young P, Fürst DO, et al. Structural basis for activation of the titin kinase domain during myofibrillogenesis. Nature. 1998;395: 863–869. doi: 10.1038/27603 9804419

7. Lange S, Xiang F, Yakovenko A, Vihola A, Hackman P, Rostkova E, et al. Cell biology: The kinase domain of titin controls muscle gene expression and protein turnover. Science (80-). 2005;308: 1599–1603. doi: 10.1126/science.1110463 15802564

8. Bogomolovas J, Gasch A, Simkovic F, Rigden DJ, Labeit S, Mayans O. Titin kinase is an inactive pseudokinase scaffold that supports MuRF1 recruitment to the sarcomeric M-line. Open Biol. 2014;4: 140041. doi: 10.1098/rsob.140041 24850911

9. Agarkova I, Perriard J-C. The M-band: an elastic web that crosslinks thick filaments in the center of the sarcomere. Trends Cell Biol. 2005;15: 477–485. doi: 10.1016/j.tcb.2005.07.001 16061384

10. Hu L-YR, Ackermann MA, Kontrogianni-Konstantopoulos A. The Sarcomeric M-Region: A Molecular Command Center for Diverse Cellular Processes. Biomed Res Int. 2015;2015: 1–25. doi: 10.1155/2015/714197 25961035

11. Bang ML, Centner T, Fornoff F, Geach a J, Gotthardt M, McNabb M, et al. The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system. Circ Res. 2001;89: 1065–72. doi: 10.1161/hh2301.100981 11717165

12. Witt CC, Olivieri N, Centner T, Kolmerer B, Millevoi S, Morell J, et al. A survey of the primary structure and the interspecies conservation of I-band titin’s elastic elements in vertebrates. J Struct Biol. 1998;122: 206–15. doi: 10.1006/jsbi.1998.3993 9724622

13. Mrosek M, Labeit D, Witt S, Heerklotz H, von Castelmur E, Labeit S, et al. Molecular determinants for the recruitment of the ubiquitin-ligase MuRF-1 onto M-line titin. FASEB J. 2007;21: 1383–1392. doi: 10.1096/fj.06-7644com 17215480

14. Steward A, Chen Q, Chapman RI, Borgia MB, Rogers JM, Wojtala A, et al. Two immunoglobulin tandem proteins with a linking β-strand reveal unexpected differences in cooperativity and folding pathways. J Mol Biol. 2012;416: 137–47. doi: 10.1016/j.jmb.2011.12.012 22197372

15. Pernigo S, Fukuzawa A, Bertz M, Holt M, Rief M, Steiner RA, et al. Structural insight into M-band assembly and mechanics from the titin-obscurin-like-1 complex. Proc Natl Acad Sci U S A. 2010;107: 2908–13. doi: 10.1073/pnas.0913736107 20133654

16. Pernigo S, Fukuzawa A, Pandini A, Holt M, Kleinjung J, Gautel M, et al. The crystal structure of the human titin:obscurin complex reveals a conserved yet specific muscle M-band zipper module. J Mol Biol. 2015;427: 718–736. doi: 10.1016/j.jmb.2014.11.019 25490259

17. Pernigo S, Fukuzawa A, Beedle AEM, Holt M, Round A, Pandini A, et al. Binding of Myomesin to Obscurin-Like-1 at the Muscle M-Band Provides a Strategy for Isoform-Specific Mechanical Protection. Structure. 2017;25: 107–120. doi: 10.1016/j.str.2016.11.015 27989621

18. Pfuhl M, Pastore A. Tertiary structure of an immunoglobulin-like domain from the giant muscle protein titin: a new member of the I set. Structure. 1995;3: 391–401. doi: 10.1016/s0969-2126(01)00170-8 7613868

19. Pfuhl M, Improta S, Politou AS, Pastore A. When a module is also a domain: The role of the N terminus in the stability and the dynamics of immunoglobulin domains from titin. J Mol Biol. 1997;265: 242–256. doi: 10.1006/jmbi.1996.0725 9020985

20. Sauer F, Vahokoski J, Song Y-H, Wilmanns M. Molecular basis of the head-to-tail assembly of giant muscle proteins obscurin-like 1 and titin. EMBO Rep. 2010;11: 534–540. doi: 10.1038/embor.2010.65 20489725

21. Prudner BC, Roy PS, Damron DS, Russell MA. $\alpha{\$}-Synemin localizes to the M-band of the sarcomere through interaction with the M10 region of titin. FEBS Lett. 2014;588: 4625–4630. doi: 10.1016/j.febslet.2014.11.001 25447537

22. Sarparanta J, Blandin G, Charton K, Vihola A, Marchand S, Milic A, et al. Interactions with M-band titin and calpain 3 link myospryn (CMYA5) to tibial and limb-girdle muscular dystrophies. J Biol Chem. 2010;285: 30304–30315. doi: 10.1074/jbc.M110.108720 20634290

23. Kinbara K, Sorimachi H, Ishiura S, Suzuki K. Muscle-Specific Calpain, p94, Interacts with the Extreme C-Terminal Region of Connectin, a Unique Region Flanked by Two Immunoglobulin C2 Motifs. Arch Biochem Biophys. 1997;342: 99–107. doi: 10.1006/abbi.1997.0108 9185618

24. Lange S, Auerbach D, McLoughlin P, Perriard E, Schäfer BW, Perriard J-C, et al. Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2. J Cell Sci. 2002;115: 4925–36. doi: 10.1242/jcs.00181 12432079

25. Gautel M, Leonard K, Labeit S. Phosphorylation of KSP motifs in the C-terminal region of titin in differentiating myoblasts. EMBO J. 1993;12: 3827–3834. doi: 10.1002/j.1460-2075.1993.tb06061.x 8404852

26. Fernando P, Sandoz JS, Ding W, de Repentigny Y, Brunette S, Kelly JF, et al. Bin1 SRC homology 3 domain acts as a scaffold for myofiber sarcomere assembly. J Biol Chem. 2009;284: 27674–86. doi: 10.1074/jbc.M109.029538 19633357

27. Luther P, Squire J. Three-dimensional structure of the vertebrate muscle M-region. J Mol Biol. 1978;125: 313–324. doi: 10.1016/0022-2836(78)90405-9 731697

28. Chauveau C, Bonnemann CG, Julien C, Kho ALAL, Marks H, Talim B, et al. Recessive TTN truncating mutations define novel forms of core myopathy with heart disease. Hum Mol Genet. 2014;23: 980–991. doi: 10.1093/hmg/ddt494 24105469

29. Ware JS, Cook SA. Role of titin in cardiomyopathy: from DNA variants to patient stratification. Nat Rev Cardiol. 2017;15: 241–252. doi: 10.1038/nrcardio.2017.190 29238064

30. Charton K, Sarparanta J, Vihola A, Milic A, Jonson PH, Suel L, et al. CAPN3-mediated processing of C-terminal titin replaced by pathological cleavage in titinopathy. Hum Mol Genet. 2015;24: 3718–3731. doi: 10.1093/hmg/ddv116 25877298

31. Kabsch W. Integration, scaling, space-group assignment and post-refinement. Acta Crystallogr Sect D Biol Crystallogr. 2010;66: 133–144. doi: 10.1107/S0907444909047374 20124693

32. Evans P. Scaling and assessment of data quality. Acta Crystallographica Section D: Biological Crystallography. 2006. pp. 72–82. doi: 10.1107/S0907444905036693 16369096

33. Evans PR, Murshudov GN. How good are my data and what is the resolution? Acta Crystallogr Sect D Biol Crystallogr. 2013;69: 1204–1214. doi: 10.1107/S0907444913000061 23793146

34. Claude JB, Suhre K, Notredame C, Claverie JM, Abergel C. CaspR: A web server for automated molecular replacement using homology modelling. Nucleic Acids Res. 2004;32: W606–W609. doi: 10.1093/nar/gkh400 15215460

35. Fiser A, Šali A. MODELLER: Generation and Refinement of Homology-Based Protein Structure Models [Internet]. Methods in Enzymology. 2003. pp. 461–491. doi: 10.1016/S0076-6879(03)74020-8

36. Murshudov GN, Vagin AA, Dodson EJ. Refinement of macromolecular structures by the maximum-likelihood method [Internet]. Acta Crystallographica Section D: Biological Crystallography. 1997. pp. 240–255. doi: 10.1107/S0907444996012255 15299926

37. McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn MD, Storoni LC, Read RJ. Phaser crystallographic software. J Appl Crystallogr. 2007;40: 658–674. doi: 10.1107/S0021889807021206 19461840

38. Terwilliger TC, Grosse-Kunstleve RW, Afonine P V., Moriarty NW, Zwart PH, Hung L-W, et al. Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard. Acta Crystallogr Sect D Biol Crystallogr. 2008;64: 61–69. doi: 10.1107/S090744490705024X 18094468

39. Adams PD, Afonine P V., Bunkóczi G, Chen VB, Davis IW, Echols N, et al. PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr Sect D Biol Crystallogr. 2010;66: 213–221. doi: 10.1107/S0907444909052925 20124702

40. Schneider TR, Sheldrick GM. Substructure solution with SHELXD. Acta Crystallogr Sect D Biol Crystallogr. 2002;58: 1772–1779. doi: 10.1107/S0907444902011678 12351820

41. Sheldrick GM. Macromolecular phasing with SHELXE. Zeitschrift fur Kristallographie. De Gruyter Oldenbourg; 2002. pp. 644–650. doi: 10.1524/zkri.217.12.644.20662

42. Langer G, Cohen SX, Lamzin VS, Perrakis A. Automated macromolecular model building for X-ray crystallography using ARP/wARP version 7. Nat Protoc. 2008;3: 1171–1179. doi: 10.1038/nprot.2008.91 18600222

43. Chen VB, Arendall WB, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr Sect D Biol Crystallogr. 2010;66: 12–21. doi: 10.1107/S0907444909042073 20057044

44. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 2018;46: W296–W303. doi: 10.1093/nar/gky427 29788355

45. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 2011;7: 539. doi: 10.1038/msb.2011.75 21988835

46. The UniProt Consortium. UniProt: A worldwide hub of protein knowledge. Nucleic Acids Res. 2019;47: D506–D515. doi: 10.1093/nar/gky1049 30395287

47. Cruickshank DWJ. Remarks about protein structure precision. Erratum. Acta Crystallogr Sect D Biol Crystallogr. 1999;55: 1108–1108. doi: 10.1107/S0907444999004308 10217697

48. Gasteiger E, Hoogland C, Gattiker A, Duvaud S, Wilkins MR, Appel RD, et al. Protein Identification and Analysis Tools on the ExPASy Server. The Proteomics Protocols Handbook. Totowa, NJ: Humana Press; 2005. pp. 571–607. doi: 10.1385/1-59259-890-0:571

49. Labeit S, Kolmerer B. Titins: Giant Proteins in Charge of Muscle Ultrastructure and Elasticity. Science (80-). 1995;270: 293–296. doi: 10.1126/science.270.5234.293 7569978

50. Harpaz Y, Chothia C. Many of the immunoglobulin superfamily domains in cell adhesion molecules and surface receptors belong to a new structural set which is close to that containing variable domains. Journal of molecular biology. 1994. pp. 528–539. doi: 10.1006/jmbi.1994.1312 8176743

51. Labeit S, Barlow DP, Gautel M, Gibson T, Holt J, Hsieh CL, et al. A regular pattern of two types of 100-residue motif in the sequence of titin. Nature. 1990;345: 273–276. doi: 10.1038/345273a0 2129545

52. Alegre-Cebollada J, Kosuri P, Giganti D, Eckels E, Rivas-Pardo JA, Hamdani N, et al. S-glutathionylation of cryptic cysteines enhances titin elasticity by blocking protein folding. Cell. 2014;156: 1235–1246. doi: 10.1016/j.cell.2014.01.056 24630725

53. Beckendorf L, Linke WA. Emerging importance of oxidative stress in regulating striated muscle elasticity. J Muscle Res Cell Motil. 2015;36: 25–36. doi: 10.1007/s10974-014-9392-y 25373878

54. Pinotsis N, Abrusci P, Djinović-Carugo K, Wilmanns M. Terminal assembly of sarcomeric filaments by intermolecular β-sheet formation. Trends Biochem Sci. 2009;34: 33–39. doi: 10.1016/j.tibs.2008.09.009 18996015

55. Giganti D, Yan K, Badilla CL, Fernandez JM, Alegre-Cebollada J. Disulfide isomerization reactions in titin immunoglobulin domains enable a mode of protein elasticity. Nat Commun. 2018;9: 185. doi: 10.1038/s41467-017-02528-7 29330363

56. Grützner A, Garcia-Manyes S, Kötter S, Badilla CL, Fernandez JM, Linke WA. Modulation of Titin-Based Stiffness by Disulfide Bonding in the Cardiac Titin N2-B Unique Sequence. Biophys J. 2009;97: 825–834. doi: 10.1016/j.bpj.2009.05.037 19651040

57. Manteca A, Schönfelder J, Alonso-Caballero A, Fertin MJ, Barruetabeña N, Faria BF, et al. Mechanochemical evolution of the giant muscle protein titin as inferred from resurrected proteins. Nat Struct Mol Biol. 2017;24: 652–657. doi: 10.1038/nsmb.3426 28671667

58. Mayans O, Wuerges J, Canela S, Gautel M, Wilmanns M. Structural Evidence for a Possible Role of Reversible Disulphide Bridge Formation in the Elasticity of the Muscle Protein Titin. Structure. 2001;9: 331–340. doi: 10.1016/s0969-2126(01)00591-3 11525170

59. Halaby DM, Poupon A, Mornon J-P. The immunoglobulin fold family: sequence analysis and 3D structure comparisons. Protein Eng Des Sel. 1999;12: 563–571. doi: 10.1093/protein/12.7.563 10436082

60. Hamill SJ, Cota E, Chothia C, Clarke J. Conservation of folding and stability within a protein family: The Tyrosine corner as an evolutionary cul-de-sac [Internet]. Journal of Molecular Biology. 2000. doi: 10.1006/jmbi.1999.3360 10623553

61. Ioerger TR, Du C, Linthicum DS. Conservation of cys–cys trp structural triads and their geometry in the protein domains of immunoglobulin superfamily members. Mol Immunol. 1999;36: 373–386. doi: 10.1016/s0161-5890(99)00032-2 10444001

62. Marino M, Svergun DI, Kreplak L, Konarev P V., Maco B, Labeit D, et al. Poly-Ig tandems from I-band titin share extended domain arrangements irrespective of the distinct features of their modular constituents. J Muscle Res Cell Motil. 2005;26: 355–365. doi: 10.1007/s10974-005-9017-6 16341830

63. Bruning M, Barsukov I, Franke B, Barbieri S, Volk M, Leopoldseder S, et al. The intracellular Ig fold: A robust protein scaffold for the engineering of molecular recognition. Protein Eng Des Sel. 2012;25: 205–212. doi: 10.1093/protein/gzs007 22355150

64. Marino SM, Gladyshev VN. Analysis and functional prediction of reactive cysteine residues. J Biol Chem. 2012;287: 4419–25. doi: 10.1074/jbc.R111.275578 22157013

65. Müller S, Lange S, Gautel M, Wilmanns M. Rigid Conformation of an Immunoglobulin Domain Tandem Repeat in the A-band of the Elastic Muscle Protein Titin. J Mol Biol. 2007;371: 469–480. doi: 10.1016/j.jmb.2007.05.055 17574571

66. Chauveau C, Rowell J, Ferreiro A. A rising titan: TTN review and mutation update. Hum Mutat. 2014;35: 1046–1059. doi: 10.1002/humu.22611 24980681

67. Exome Aggregation Consortium, Lek M, Karczewski K, Minikel E, Samocha K, Banks E, et al. Analysis of protein-coding genetic variation in 60,706 humans. bioRxiv. 2015; 030338. doi: 10.1101/030338

68. Laddach A, Gautel M, Fraternali F, Valencia A. TITINdb—a computational tool to assess titin’s role as a disease gene. Valencia A, editor. Bioinformatics. 2017;33: 3482–3485. doi: 10.1093/bioinformatics/btx424 29077808

69. Rudloff MW, Woosley AN, Wright NT. Biophysical characterization of naturally occurring titin M10 mutations. Protein Sci. 2015;24: 946–55. doi: 10.1002/pro.2670 25739468

70. Savarese M, Sarparanta J, Vihola A, Udd B, Hackman P. Increasing Role of Titin Mutations in Neuromuscular Disorders. J Neuromuscul Dis. 2016;3: 293–308. doi: 10.3233/JND-160158 27854229

71. Hackman P, Vihola A, Haravuori H, Marchand S, Sarparanta J, de Seze J, et al. Tibial Muscular Dystrophy Is a Titinopathy Caused by Mutations in TTN, the Gene Encoding the Giant Skeletal-Muscle Protein Titin. Am J Hum Genet. 2002;71: 492–500. doi: 10.1086/342380 12145747

72. Zheng W, Chen H, Deng X, Yuan L, Yang Y, Song Z, et al. Identification of a Novel Mutation in the Titin Gene in a Chinese Family with Limb-Girdle Muscular Dystrophy 2J. Mol Neurobiol. 2016;53: 5097–5102. doi: 10.1007/s12035-015-9439-0 26392295

73. Pollazzon M, Suominen T, Penttilä S, Malandrini A, Carluccio MA, Mondelli M, et al. The first Italian family with tibial muscular dystrophy caused by a novel titin mutation. J Neurol. 2010;257: 575–579. doi: 10.1007/s00415-009-5372-3 19911250

74. Van den Bergh PYK, Bouquiaux O, Verellen C, Marchand S, Richard I, Hackman P, et al. Tibial muscular dystrophy in a Belgian family. Ann Neurol. 2003;54: 248–251. doi: 10.1002/ana.10647 12891679

75. Evilä A, Palmio J, Vihola A, Savarese M, Tasca G, Penttilä S, et al. Targeted Next-Generation Sequencing Reveals Novel TTN Mutations Causing Recessive Distal Titinopathy. Mol Neurobiol. 2017;54: 7212–7223. doi: 10.1007/s12035-016-0242-3 27796757

76. Pires DE V., Ascher DB, Blundell TL. DUET: a server for predicting effects of mutations on protein stability using an integrated computational approach. Nucleic Acids Res. 2014;42: W314–W319. doi: 10.1093/nar/gku411 24829462

77. Sherry ST. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2001;29: 308–311. doi: 10.1093/nar/29.1.308 11125122