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The Ig doublet Z1Z2: a model system for the hybrid analysis of conformational dynamics in Ig tandems from titin.

Marino M, Zou P, Svergun D, Garcia P, Edlich C, Simon B, Wilmanns M, Muhle-Goll C, Mayans O
Structure 14 1437-47 (2006)
Cited: 32 times
EuropePMC logo PMID: 16962974

Abstract

Titin is a gigantic elastic filament that determines sarcomere ultrastructure and stretch response in vertebrate muscle. It folds into numerous Ig and FnIII domains connected in tandem. Data on interdomain arrangements and dynamics are essential for understanding the function of this filament. Here, we report a mechanistic analysis of the conformational dynamics of two Ig domains from the N terminus of titin, Z1Z2, by using X-ray crystallography, SAXS, NMR relaxation data, and residual dipolar couplings in combination. Z1Z2 preferentially adopts semiextended conformations in solution, with close-hinge arrangements representing low-probability states. Although interdomain contacts are not observed, the linker appears to acquire moderate rigidity via small, local hydrophobic interactions. Thus, Z1Z2 constitutes an adaptable modular system with restricted dynamics. We speculate that its preexistent conformation contributes to the selective recruitment of the binding partner telethonin onto the repetitive surface of the filament. The structural interconversion of four Z1Z2 conformers is analyzed.

Reviews - 2a38 mentioned but not cited (1)

  1. The ZT Biopolymer: A Self-Assembling Protein Scaffold for Stem Cell Applications. Nesterenko Y, Hill CJ, Fleming JR, Murray P, Mayans O. Int J Mol Sci 20 4299 (2019)

Articles - 2a38 mentioned but not cited (5)

  1. Secondary and tertiary structure elasticity of titin Z1Z2 and a titin chain model. Lee EH, Hsin J, Mayans O, Schulten K. Biophys J 93 1719-1735 (2007)
  2. Rapid automated superposition of shapes and macromolecular models using spherical harmonics. Konarev PV, Petoukhov MV, Svergun DI. J Appl Crystallogr 49 953-960 (2016)
  3. Making sense of missense variants in TTN-related congenital myopathies. Rees M, Nikoopour R, Fukuzawa A, Kho AL, Fernandez-Garcia MA, Wraige E, Bodi I, Deshpande C, Özdemir Ö, Daimagüler HS, Pfuhl M, Holt M, Brandmeier B, Grover S, Fluss J, Longman C, Farrugia ME, Matthews E, Hanna M, Muntoni F, Sarkozy A, Phadke R, Quinlivan R, Oates EC, Schröder R, Thiel C, Reimann J, Voermans N, Erasmus C, Kamsteeg EJ, Konersman C, Grosmann C, McKee S, Tirupathi S, Moore SA, Wilichowski E, Hobbiebrunken E, Dekomien G, Richard I, Van den Bergh P, Domínguez-González C, Cirak S, Ferreiro A, Jungbluth H, Gautel M. Acta Neuropathol 141 431-453 (2021)
  4. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  5. Molecular insights into titin's A-band. Fleming JR, Müller I, Zacharchenko T, Diederichs K, Mayans O. J Muscle Res Cell Motil 44 255-270 (2023)


Reviews citing this publication (8)

  1. X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution. Putnam CD, Hammel M, Hura GL, Tainer JA. Q Rev Biophys 40 191-285 (2007)
  2. The giant protein titin: a regulatory node that integrates myocyte signaling pathways. Krüger M, Linke WA. J Biol Chem 286 9905-9912 (2011)
  3. NMR approaches for structural analysis of multidomain proteins and complexes in solution. Göbl C, Madl T, Simon B, Sattler M. Prog Nucl Magn Reson Spectrosc 80 26-63 (2014)
  4. Applications of small-angle X-ray scattering to biomacromolecular solutions. Petoukhov MV, Svergun DI. Int J Biochem Cell Biol 45 429-437 (2013)
  5. Roles of titin in the structure and elasticity of the sarcomere. Tskhovrebova L, Trinick J. J Biomed Biotechnol 2010 612482 (2010)
  6. Molecular origin of the hierarchical elasticity of titin: simulation, experiment, and theory. Hsin J, Strümpfer J, Lee EH, Schulten K. Annu Rev Biophys 40 187-203 (2011)
  7. Structure of giant muscle proteins. Meyer LC, Wright NT. Front Physiol 4 368 (2013)
  8. Terminal assembly of sarcomeric filaments by intermolecular beta-sheet formation. Pinotsis N, Abrusci P, Djinović-Carugo K, Wilmanns M. Trends Biochem Sci 34 33-39 (2009)

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  2. Molecular determinants for the recruitment of the ubiquitin-ligase MuRF-1 onto M-line titin. Mrosek M, Labeit D, Witt S, Heerklotz H, von Castelmur E, Labeit S, Mayans O. FASEB J 21 1383-1392 (2007)
  3. Effect of interdomain dynamics on the structure determination of modular proteins by small-angle scattering. Bernadó P. Eur Biophys J 39 769-780 (2010)
  4. Refined solution structure of the 82-kDa enzyme malate synthase G from joint NMR and synchrotron SAXS restraints. Grishaev A, Tugarinov V, Kay LE, Trewhella J, Bax A. J Biomol NMR 40 95-106 (2008)
  5. A regular pattern of Ig super-motifs defines segmental flexibility as the elastic mechanism of the titin chain. von Castelmur E, Marino M, Svergun DI, Kreplak L, Ucurum-Fotiadis Z, Konarev PV, Urzhumtsev A, Labeit D, Labeit S, Mayans O. Proc Natl Acad Sci U S A 105 1186-1191 (2008)
  6. A structure refinement protocol combining NMR residual dipolar couplings and small angle scattering restraints. Gabel F, Simon B, Nilges M, Petoukhov M, Svergun D, Sattler M. J Biomol NMR 41 199-208 (2008)
  7. NMR and small-angle scattering-based structural analysis of protein complexes in solution. Madl T, Gabel F, Sattler M. J Struct Biol 173 472-482 (2011)
  8. Rigid conformation of an immunoglobulin domain tandem repeat in the A-band of the elastic muscle protein titin. Müller S, Lange S, Gautel M, Wilmanns M. J Mol Biol 371 469-480 (2007)
  9. The structure of the FnIII Tandem A77-A78 points to a periodically conserved architecture in the myosin-binding region of titin. Bucher RM, Svergun DI, Muhle-Goll C, Mayans O. J Mol Biol 401 843-853 (2010)
  10. Spontaneous dimerization of titin protein Z1Z2 domains induces strong nanomechanical anchoring. Garcia-Manyes S, Badilla CL, Alegre-Cebollada J, Javadi Y, Fernández JM. J Biol Chem 287 20240-20247 (2012)
  11. The N2A region of titin has a unique structural configuration. Stronczek C, Lange S, Bullard B, Wolniak S, Börgeson E, Mayans O, Fleming JR. J Gen Physiol 153 e202012766 (2021)
  12. A simple procedure to evaluate the efficiency of bio-macromolecular rigid-body refinement by small-angle scattering. Gabel F. Eur Biophys J 41 1-11 (2012)
  13. Conformational plasticity and evolutionary analysis of the myotilin tandem Ig domains. Puž V, Pavšič M, Lenarčič B, Djinović-Carugo K. Sci Rep 7 3993 (2017)
  14. Dynamic strength of titin's Z-disk end. Kollár V, Szatmári D, Grama L, Kellermayer MS. J Biomed Biotechnol 2010 838530 (2010)
  15. The intracellular Ig fold: a robust protein scaffold for the engineering of molecular recognition. Bruning M, Barsukov I, Franke B, Barbieri S, Volk M, Leopoldseder S, Ucurum Z, Mayans O. Protein Eng Des Sel 25 205-212 (2012)
  16. Molecular investigations into the mechanics of a muscle anchoring complex. Bodmer NK, Theisen KE, Dima RI. Biophys J 108 2322-2332 (2015)
  17. Pairwise sequence similarity mapping with PaSiMap: Reclassification of immunoglobulin domains from titin as case study. Su K, Mayans O, Diederichs K, Fleming JR. Comput Struct Biotechnol J 20 5409-5419 (2022)
  18. Self-Assembling Proteins as High-Performance Substrates for Embryonic Stem Cell Self-Renewal. Hill CJ, Fleming JR, Mousavinejad M, Nicholson R, Tzokov SB, Bullough PA, Bogomolovas J, Morgan MR, Mayans O, Murray P. Adv Mater 31 e1807521 (2019)


Related citations provided by authors (1)

  1. Secondary and tertiary structure elasticity of titin Z1Z2 and a titin chain model.. Lee EH, Hsin J, Mayans O, Schulten K Biophys J 93 1719-35 (2007)

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