Native topology determines force-induced unfolding pathways in globular proteins

被引:144
作者
Klimov, DK [1 ]
Thirumalai, D
机构
[1] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA
[2] Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA
关键词
D O I
10.1073/pnas.97.13.7254
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Single-molecule manipulation techniques reveal that stretching unravels individually folded domains in the muscle protein titin and the extracellular matrix protein tenascin. These elastic proteins contain tandem repeats of folded domains with beta-sandwich architecture. Herein, we propose by stretching two model sequences (S1 and S2) with four-stranded beta-barrel topology that unfolding forces and pathways in folded domains can be predicted by using only the structure of the native state. Thermal refolding of S1 and SZ in the absence of force proceeds in an all-or-none fashion. In contrast, phase diagrams in the force-temperature (f,T) plane and steered Langevin dynamics studies of these sequences, which differ in the native registry of the strands, show that S1 unfolds in an all-or-none fashion, whereas unfolding of S2 occurs via an obligatory intermediate. Force-induced unfolding is determined by the native topology. After proving that the simulation results for S1 and S2 can he calculated by using native topology alone, we predict the order of unfolding events in Ig domain (Ig27) and two fibronectin ill type domains ((9)FnIII and (10)FnIII). The calculated unfolding pathways for these proteins, the location of the transition states, and the pulling speed dependence of the unfolding forces reflect the differences in the way the strands are arranged in the native states. We also predict the mechanisms of force-induced unfolding of the coiled-coil spectrin (a three-helix bundle protein) for all 20 structures deposited in the Protein Data Bank. Our approach suggests a natural way to measure the phase diagram in the (f,C) plane, where C is the concentration of denaturants.
引用
收藏
页码:7254 / 7259
页数:6
相关论文
共 50 条
  • [31] Probing force-induced unfolding intermediates of a single staphylococcal nuclease molecule and the effect of ligand binding
    Ishii, Takaaki
    Murayama, Yoshihiro
    Katano, Atsuto
    Maki, Kosuke
    Kuwajima, Kunihiro
    Sano, Masaki
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 375 (04) : 586 - 591
  • [32] Cooperativity in Thermal and Force-Induced Protein Unfolding: Integration of Crack Propagation and Network Elasticity Models
    Srivastava, Amit
    Granek, Rony
    PHYSICAL REVIEW LETTERS, 2013, 110 (13)
  • [33] Force-Induced Unfolding of Leucine-Rich Repeats of Glycoprotein Ibα Strengthens Ligand Interaction
    Ju, Lining
    Lou, Jizhong
    Chen, Yunfeng
    Li, Zhenhai
    Zhu, Cheng
    BIOPHYSICAL JOURNAL, 2015, 109 (09) : 1781 - 1784
  • [34] Cross-correlation analysis to salt-bridge dynamics in force-induced unfolding of titin kinase
    Wu, Ming-Chya
    Forbes, Jeffrey G.
    Wang, Kuan
    2011 21ST INTERNATIONAL CONFERENCE ON NOISE AND FLUCTUATIONS (ICNF), 2011, : 429 - 432
  • [35] Force-induced unfolding of a homopolymer on a fractal lattice: exact results versus mean-field predictions
    Marenduzzo, D
    Maritan, A
    Seno, F
    JOURNAL OF PHYSICS A-MATHEMATICAL AND GENERAL, 2002, 35 (18): : L233 - L240
  • [36] Force-induced unfolding of human telomeric G-quadruplex: A steered molecular dynamics simulation study
    Li, Hui
    Cao, En-hua
    Gisler, Thomas
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2009, 379 (01) : 70 - 75
  • [37] Unfolding proteins with an atomic force microscope: Force-fluctuation-induced nonexponential kinetics
    Clusel, Maxime
    Corwin, Eric I.
    PHYSICAL REVIEW E, 2011, 84 (04):
  • [38] PHYS 67-Force-clamp studies of the folding/unfolding pathways of single proteins
    Fernandez, Julio M.
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2006, 232
  • [39] Reconstruction of mechanical unfolding and refolding pathways of proteins with atomic force spectroscopy and computer simulations
    Li, Qing
    Apostolidou, Dimitra
    Marszalek, Piotr E.
    METHODS, 2022, 197 : 39 - 53
  • [40] Force-induced melting and S-DNA pathways for DNA overstretching exhibit distinct kinetics
    Rajan, Vinoth Sundar
    Levin, Sune
    Mccauley, Micah J.
    Williams, Mark C.
    Rouzina, Ioulia
    Wilhelmsson, L. Marcus
    Westerlund, Fredrik
    NUCLEIC ACIDS RESEARCH, 2024, 53 (01)