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PMID: 16227505 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Extending a spectrin repeat unit. II: rupture behavior.

Biophysical journal ·Vol. 90 ·No. 1 ·2006-01-01 ·Pages 101-11

Paramore S, Ayton GS, Voth GA

Abstract

A spectrin repeat unit was subject to extension using cyclic expansion nonequilibrium molecular dynamics. Periodic boundary conditions were used to examine the effects of the contiguous alpha-helical linker on the force response. The measured force-extension curve shows a linear increase in the force response when the spectrin repeat unit is extended by approximately 0.4 nm. After that point, the force response peaks and subsequently declines. The peak in the force response marks the point where the spectrin repeat unit undergoes a change in its material properties from a strongly elastic material to a mostly viscous one, on the timescales of the simulations. The force peak is also correlated with rupture of the alpha-helical linker, and is likely the event responsible for the peaks in the sawtooth-pattern force-extension curves measured by atomic force microscopy experiments. Rupture of the linker involves simultaneously breaking approximately four hydrogen bonds that maintain the alpha-helical linker. After this initial rupture, the linker undergoes simple helix-to-coil transitions as the spectrin repeat unit continues to be extended. The implications of linker rupture in the interpretation of unfolding and atomic force microscopy experiments are also discussed.

MeSH Terms
Animals Brain/metabolism Chickens Computer Simulation Hydrogen Bonding Microscopy, Atomic Force Models, Molecular Molecular Conformation Protein Conformation Protein Denaturation Protein Folding Protein Structure, Secondary Protein Structure, Tertiary Software Spectrin/chemistry Time Factors
Chemicals
Spectrin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Paramore Sterling
Center for Biophysical Modeling and Simulation and Department of Chemistry, University of Utah, Salt Lake City, Utah, USA.
Ayton Gary S
Voth Gregory A
References (40)
40 references, click to expand
  1. Phasing the conformational unit of spectrin.
    Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10788-91 PMID: 1961746
  2. Entropic barriers, transition states, funnels, and exponential protein folding kinetics: a simple model.
    Protein Sci. 2000 Mar;9(3):452-65 PMID: 10752607
  3. Crystal structure of the repetitive segments of spectrin.
    Science. 1993 Dec 24;262(5142):2027-30 PMID: 8266097
  4. Elasticity and unfolding of single molecules of the giant muscle protein titin.
    Nature. 1997 May 15;387(6630):308-12 PMID: 9153398
  5. Kinetics from nonequilibrium single-molecule pulling experiments.
    Biophys J. 2003 Jul;85(1):5-15 PMID: 12829459
  6. Free energies of urea and of thermal unfolding show that two tandem repeats of spectrin are thermodynamically more stable than a single repeat.
    Biochemistry. 2001 Apr 3;40(13):3974-84 PMID: 11300778
  7. The molecular elasticity of the extracellular matrix protein tenascin.
    Nature. 1998 May 14;393(6681):181-5 PMID: 9603523
  8. The key event in force-induced unfolding of Titin's immunoglobulin domains.
    Biophys J. 2000 Jul;79(1):51-65 PMID: 10866937
  9. Erythrocyte spectrin is comprised of many homologous triple helical segments.
    Nature. 1984 Sep 13-19;311(5982):177-80 PMID: 6472478
  10. Primary structure of the brain alpha-spectrin.
    J Cell Biol. 1989 Jan;108(1):79-93 PMID: 2910879
  11. Calculating the bulk modulus for a lipid bilayer with nonequilibrium molecular dynamics simulation.
    Biophys J. 2002 Mar;82(3):1226-38 PMID: 11867440
  12. Extending a spectrin repeat unit. I: linear force-extension response.
    Biophys J. 2006 Jan 1;90(1):92-100 PMID: 16227506
  13. Structural insights into the stability and flexibility of unusual erythroid spectrin repeats.
    Structure. 2004 Apr;12(4):645-56 PMID: 15062087
  14. Pathway shifts and thermal softening in temperature-coupled forced unfolding of spectrin domains.
    Biophys J. 2003 Nov;85(5):3286-93 PMID: 14581229
  15. Unfolding a linker between helical repeats.
    J Mol Biol. 2005 Jun 10;349(3):638-47 PMID: 15896349
  16. Reversible unfolding of individual titin immunoglobulin domains by AFM.
    Science. 1997 May 16;276(5315):1109-12 PMID: 9148804
  17. Ligand binding: molecular mechanics calculation of the streptavidin-biotin rupture force.
    Science. 1996 Feb 16;271(5251):997-9 PMID: 8584939
  18. Structure of the alpha-actinin rod: molecular basis for cross-linking of actin filaments.
    Cell. 1999 Aug 20;98(4):537-46 PMID: 10481917
  19. Steered molecular dynamics simulations of force-induced protein domain unfolding.
    Proteins. 1999 Jun 1;35(4):453-63 PMID: 10382673
  20. Single molecule force spectroscopy of spectrin repeats: low unfolding forces in helix bundles.
    J Mol Biol. 1999 Feb 19;286(2):553-61 PMID: 9973570
  21. Solution structure of the spectrin repeat: a left-handed antiparallel triple-helical coiled-coil.
    J Mol Biol. 1997 Oct 31;273(3):740-51 PMID: 9356261
  22. States and transitions during forced unfolding of a single spectrin repeat.
    FEBS Lett. 2000 Jul 7;476(3):124-8 PMID: 10913598
  23. Molecular dynamics study of unbinding of the avidin-biotin complex.
    Biophys J. 1997 Apr;72(4):1568-81 PMID: 9083662
  24. Forced unfolding of the fibronectin type III module reveals a tensile molecular recognition switch.
    Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1351-6 PMID: 9990027
  25. Pathways and intermediates in forced unfolding of spectrin repeats.
    Structure. 2002 Aug;10(8):1085-96 PMID: 12176386
  26. Cooperativity in forced unfolding of tandem spectrin repeats.
    Biophys J. 2003 Jan;84(1):533-44 PMID: 12524305
  27. The study of protein mechanics with the atomic force microscope.
    Trends Biochem Sci. 1999 Oct;24(10):379-84 PMID: 10500301
  28. VMD: visual molecular dynamics.
    J Mol Graph. 1996 Feb;14(1):33-8, 27-8 PMID: 8744570
  29. Interfacing molecular dynamics and macro-scale simulations for lipid bilayer vesicles.
    Biophys J. 2002 Aug;83(2):1026-38 PMID: 12124284
  30. Structures of two repeats of spectrin suggest models of flexibility.
    Cell. 1999 Aug 20;98(4):523-35 PMID: 10481916
  31. Crystal structure of the alpha-actinin rod reveals an extensive torsional twist.
    Structure. 2001 Jul 3;9(7):597-604 PMID: 11470434
  32. Stabilities of folding of clustered, two-repeat fragments of spectrin reveal a potential hinge in the human erythroid spectrin tetramer.
    Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1502-7 PMID: 14747656
  33. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling.
    Electrophoresis. 1997 Dec;18(15):2714-23 PMID: 9504803
  34. A model of spectrin as a concertina in the erythrocyte membrane skeleton.
    Trends Cell Biol. 1992 Jul;2(7):186-9 PMID: 14731498
  35. Relating single-molecule measurements to thermodynamics.
    Biophys J. 2003 Feb;84(2 Pt 1):733-8 PMID: 12547757
  36. The mechanical stability of immunoglobulin and fibronectin III domains in the muscle protein titin measured by atomic force microscopy.
    Biophys J. 1998 Dec;75(6):3008-14 PMID: 9826620
  37. Unfolding proteins by external forces and temperature: the importance of topology and energetics.
    Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6521-6 PMID: 10823892
  38. Independent movement, dimerization and stability of tandem repeats of chicken brain alpha-spectrin.
    J Mol Biol. 2004 Nov 19;344(2):495-511 PMID: 15522301
  39. Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation.
    Biophys J. 1998 Aug;75(2):662-71 PMID: 9675168
  40. Mechanical unfolding of a titin Ig domain: structure of transition state revealed by combining atomic force microscopy, protein engineering and molecular dynamics simulations.
    J Mol Biol. 2003 Jul 18;330(4):867-77 PMID: 12850153
Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
Published
2006-01-01
Epub
2005-00-14
Pages
101-11
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1367010
Subset
IM
Grants
NCRR NIH HHS · 1 S10 RR17214-01 · United States
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