메뉴 건너뛰기




Volumn 153, Issue 1, 2010, Pages 1-8

The effect of shear stress on protein conformation: Physical forces operating on biochemical systems: The case of von Willebrand factor

Author keywords

Blood haemostasis; Protein conformational changes; Shear stress; Vicinal cysteines disulfide bond; Von Willebrand factor

Indexed keywords

BOTROCETIN; DORNASE ALFA; GLYCOPEPTIDE; HUMAN GROWTH HORMONE; POLYPHENOL; RISTOCETIN; VON WILLEBRAND FACTOR;

EID: 78649756268     PISSN: 03014622     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bpc.2010.07.002     Document Type: Review
Times cited : (82)

References (73)
  • 5
    • 66749101666 scopus 로고    scopus 로고
    • Biochemistry. Force signaling in biology
    • J.C. Gebhardt, and M. Rief Biochemistry. Force signaling in biology Science 324 2009 1278 1280
    • (2009) Science , vol.324 , pp. 1278-1280
    • Gebhardt, J.C.1    Rief, M.2
  • 6
    • 0036624844 scopus 로고    scopus 로고
    • Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: Studies using optical tweezers
    • M. Arya, B. Anvari, G.M. Romo, M.A. Cruz, J.F. Dong, L.V. McIntire, J.L. Moake, and J.A. Lopez Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers Blood 99 2002 3971 3977
    • (2002) Blood , vol.99 , pp. 3971-3977
    • Arya, M.1    Anvari, B.2    Romo, G.M.3    Cruz, M.A.4    Dong, J.F.5    McIntire, L.V.6    Moake, J.L.7    Lopez, J.A.8
  • 7
    • 33846592202 scopus 로고    scopus 로고
    • Conformational stability and domain unfolding of the von Willebrand factor A domains
    • M. Auton, M.A. Cruz, and J. Moake Conformational stability and domain unfolding of the Von Willebrand factor A domains J. Mol. Biol. 366 2007 986 1000
    • (2007) J. Mol. Biol. , vol.366 , pp. 986-1000
    • Auton, M.1    Cruz, M.A.2    Moake, J.3
  • 8
    • 70349289438 scopus 로고    scopus 로고
    • Urea-mediated protein denaturation: A consensus view
    • A. Das, and C. Mukhopadhyay Urea-mediated protein denaturation: a consensus view J. Phys. Chem. B 113 2009 12816 12824
    • (2009) J. Phys. Chem. B , vol.113 , pp. 12816-12824
    • Das, A.1    Mukhopadhyay, C.2
  • 14
    • 0029917453 scopus 로고    scopus 로고
    • Increased shear stress overcomes the antithrombotic platelet inhibitory effect of aspirin in stenosed dog coronary arteries
    • N. Maalej, and J.D. Folts Increased shear stress overcomes the antithrombotic platelet inhibitory effect of aspirin in stenosed dog coronary arteries Circulation 93 1996 1201 1205
    • (1996) Circulation , vol.93 , pp. 1201-1205
    • Maalej, N.1    Folts, J.D.2
  • 16
    • 0346688700 scopus 로고    scopus 로고
    • Hydrodynamic forces applied on intercellular bonds, soluble molecules, and cell-surface receptors
    • H. Shankaran, and S. Neelamegham Hydrodynamic forces applied on intercellular bonds, soluble molecules, and cell-surface receptors Biophys. J. 86 2004 576 588
    • (2004) Biophys. J. , vol.86 , pp. 576-588
    • Shankaran, H.1    Neelamegham, S.2
  • 18
    • 0008884532 scopus 로고
    • Slow viscous motion of a sphere parallel to a plane wall-II couvette flow
    • A.J. Goldman, R.G. Cox, and H. Brenner Slow viscous motion of a sphere parallel to a plane wall-II couvette flow Chem. Eng. Sci. 22 1967 653 660
    • (1967) Chem. Eng. Sci. , vol.22 , pp. 653-660
    • Goldman, A.J.1    Cox, R.G.2    Brenner, H.3
  • 19
    • 0002793168 scopus 로고
    • The kinetics of flowing dispersions, VIII. Doublets of rigid spheres (theoretical)
    • M.S.G. Arp P.A., The kinetics of flowing dispersions, VIII. Doublets of rigid spheres (theoretical), J. Coll. Interf. Sci, 61 (1977) 21-43.
    • (1977) J. Coll. Interf. Sci , vol.61 , pp. 21-43
    • Arp, M.S.G.1    A, P.2
  • 20
    • 0014718113 scopus 로고
    • Protein denaturation. C. Theoretical models for the mechanism of denaturation
    • C. Tanford Protein denaturation. C. Theoretical models for the mechanism of denaturation Adv. Protein Chem. 24 1970 1 95
    • (1970) Adv. Protein Chem. , vol.24 , pp. 1-95
    • Tanford, C.1
  • 21
    • 0027123099 scopus 로고
    • Protein folding. Up the kinetic pathway
    • T.E. Creighton Protein folding. Up the kinetic pathway Nature 356 1992 194 195
    • (1992) Nature , vol.356 , pp. 194-195
    • Creighton, T.E.1
  • 26
    • 9544258376 scopus 로고    scopus 로고
    • Effect of high shear on proteins
    • Y.F. Maa, and C.C. Hsu Effect of high shear on proteins Biotechnol. Bioeng. 51 1996 458 465
    • (1996) Biotechnol. Bioeng. , vol.51 , pp. 458-465
    • Maa, Y.F.1    Hsu, C.C.2
  • 27
    • 33751244556 scopus 로고    scopus 로고
    • Do protein molecules unfold in a simple shear flow?
    • J. Jaspe, and S.J. Hagen Do protein molecules unfold in a simple shear flow? Biophys. J. 91 2006 3415 3424
    • (2006) Biophys. J. , vol.91 , pp. 3415-3424
    • Jaspe, J.1    Hagen, S.J.2
  • 31
    • 66149107458 scopus 로고    scopus 로고
    • Fluid shear induces conformation change in human blood protein von Willebrand factor in solution
    • I. Singh, E. Themistou, L. Porcar, and S. Neelamegham Fluid shear induces conformation change in human blood protein von Willebrand factor in solution Biophys. J. 96 2009 2313 2320
    • (2009) Biophys. J. , vol.96 , pp. 2313-2320
    • Singh, I.1    Themistou, E.2    Porcar, L.3    Neelamegham, S.4
  • 32
    • 72249086229 scopus 로고    scopus 로고
    • Application of fluorescence spectroscopy to quantify shear-induced protein conformation change
    • E. Themistou, I. Singh, C. Shang, S.V. Balu-Iyer, P. Alexandridis, and S. Neelamegham Application of fluorescence spectroscopy to quantify shear-induced protein conformation change Biophys. J. 97 2009 2567 2576
    • (2009) Biophys. J. , vol.97 , pp. 2567-2576
    • Themistou, E.1    Singh, I.2    Shang, C.3    Balu-Iyer, S.V.4    Alexandridis, P.5    Neelamegham, S.6
  • 33
    • 0034646604 scopus 로고    scopus 로고
    • Localization of von Willebrand factor-binding sites for platelet glycoprotein Ib and botrocetin by charged-to-alanine scanning mutagenesis
    • T. Matsushita, D. Meyer, and J.E. Sadler Localization of von Willebrand factor-binding sites for platelet glycoprotein Ib and botrocetin by charged-to-alanine scanning mutagenesis J. Biol. Chem. 275 2000 11044 11049
    • (2000) J. Biol. Chem. , vol.275 , pp. 11044-11049
    • Matsushita, T.1    Meyer, D.2    Sadler, J.E.3
  • 34
    • 0018770590 scopus 로고
    • Human blood platelet adhesion to artery subendothelium is mediated by factor VIII-Von Willebrand factor bound to the subendothelium
    • K.S. Sakariassen, P.A. Bolhuis, and J.J. Sixma Human blood platelet adhesion to artery subendothelium is mediated by factor VIII-Von Willebrand factor bound to the subendothelium Nature 279 1979 636 638
    • (1979) Nature , vol.279 , pp. 636-638
    • Sakariassen, K.S.1    Bolhuis, P.A.2    Sixma, J.J.3
  • 35
    • 0031686041 scopus 로고    scopus 로고
    • Biochemistry and genetics of von Willebrand factor
    • J.E. Sadler Biochemistry and genetics of von Willebrand factor Annu. Rev. Biochem. 67 1998 395 424
    • (1998) Annu. Rev. Biochem. , vol.67 , pp. 395-424
    • Sadler, J.E.1
  • 39
    • 0029042992 scopus 로고
    • Identification of amino acid residues essential for von Willebrand factor binding to platelet glycoprotein Ib. Charged-to-alanine scanning mutagenesis of the A1 domain of human von Willebrand factor
    • T. Matsushita, and J.E. Sadler Identification of amino acid residues essential for von Willebrand factor binding to platelet glycoprotein Ib. Charged-to-alanine scanning mutagenesis of the A1 domain of human von Willebrand factor J. Biol. Chem. 270 1995 13406 13414
    • (1995) J. Biol. Chem. , vol.270 , pp. 13406-13414
    • Matsushita, T.1    Sadler, J.E.2
  • 40
    • 0027427962 scopus 로고
    • The interaction of the von Willebrand factor-A1 domain with platelet glycoprotein Ib/IX. The role of glycosylation and disulfide bonding in a monomeric recombinant A1 domain protein
    • M.A. Cruz, R.I. Handin, and R.J. Wise The interaction of the von Willebrand factor-A1 domain with platelet glycoprotein Ib/IX. The role of glycosylation and disulfide bonding in a monomeric recombinant A1 domain protein J. Biol. Chem. 268 1993 21238 21245
    • (1993) J. Biol. Chem. , vol.268 , pp. 21238-21245
    • Cruz, M.A.1    Handin, R.I.2    Wise, R.J.3
  • 41
    • 0029647484 scopus 로고
    • Interaction of the von Willebrand factor (vWF) with collagen. Localization of the primary collagen-binding site by analysis of recombinant vWF a domain polypeptides
    • M.A. Cruz, H. Yuan, J.R. Lee, R.J. Wise, and R.I. Handin Interaction of the von Willebrand factor (vWF) with collagen. Localization of the primary collagen-binding site by analysis of recombinant vWF a domain polypeptides J. Biol. Chem. 270 1995 10822 10827
    • (1995) J. Biol. Chem. , vol.270 , pp. 10822-10827
    • Cruz, M.A.1    Yuan, H.2    Lee, J.R.3    Wise, R.J.4    Handin, R.I.5
  • 42
    • 0025044664 scopus 로고
    • Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor
    • J.A. Dent, S.D. Berkowitz, J. Ware, C.K. Kasper, and Z.M. Ruggeri Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor Proc. Natl Acad. Sci. USA 87 1990 6306 6310
    • (1990) Proc. Natl Acad. Sci. USA , vol.87 , pp. 6306-6310
    • Dent, J.A.1    Berkowitz, S.D.2    Ware, J.3    Kasper, C.K.4    Ruggeri, Z.M.5
  • 43
    • 0037158606 scopus 로고    scopus 로고
    • Thrombotic microangiopathies
    • J.L. Moake Thrombotic microangiopathies N Engl J. Med. 347 2002 589 600
    • (2002) N Engl J. Med. , vol.347 , pp. 589-600
    • Moake, J.L.1
  • 44
    • 38349155217 scopus 로고    scopus 로고
    • Platelet-VWF complexes are preferred substrates of ADAMTS13 under fluid shear stress
    • K. Shim, P.J. Anderson, E.A. Tuley, E. Wiswall, and J.E. Sadler Platelet-VWF complexes are preferred substrates of ADAMTS13 under fluid shear stress Blood 111 2008 651 657
    • (2008) Blood , vol.111 , pp. 651-657
    • Shim, K.1    Anderson, P.J.2    Tuley, E.A.3    Wiswall, E.4    Sadler, J.E.5
  • 45
    • 61849116707 scopus 로고    scopus 로고
    • Integrin alpha(v)beta(3) on human endothelial cells binds von Willebrand factor strings under fluid shear stress
    • J. Huang, R. Roth, J.E. Heuser, and J.E. Sadler Integrin alpha(v)beta(3) on human endothelial cells binds von Willebrand factor strings under fluid shear stress Blood 113 2009 1589 1597
    • (2009) Blood , vol.113 , pp. 1589-1597
    • Huang, J.1    Roth, R.2    Heuser, J.E.3    Sadler, J.E.4
  • 46
    • 0019442145 scopus 로고
    • The complex multimeric composition of factor VIII/von Willebrand factor
    • Z.M. Ruggeri, and T.S. Zimmerman The complex multimeric composition of factor VIII/von Willebrand factor Blood 57 1981 1140 1143
    • (1981) Blood , vol.57 , pp. 1140-1143
    • Ruggeri, Z.M.1    Zimmerman, T.S.2
  • 47
    • 0034677986 scopus 로고    scopus 로고
    • Interaction of von Willebrand factor domain A1 with platelet glycoprotein Ibalpha-(1-289). Slow intrinsic binding kinetics mediate rapid platelet adhesion
    • S. Miura, C.Q. Li, Z. Cao, H. Wang, M.R. Wardell, and J.E. Sadler Interaction of von Willebrand factor domain A1 with platelet glycoprotein Ibalpha-(1-289). Slow intrinsic binding kinetics mediate rapid platelet adhesion J. Biol. Chem. 275 2000 7539 7546
    • (2000) J. Biol. Chem. , vol.275 , pp. 7539-7546
    • Miura, S.1    Li, C.Q.2    Cao, Z.3    Wang, H.4    Wardell, M.R.5    Sadler, J.E.6
  • 48
    • 13344295095 scopus 로고    scopus 로고
    • Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor
    • B. Savage, E. Saldivar, and Z.M. Ruggeri Initiation of platelet adhesion by arrest onto fibrinogen or translocation on von Willebrand factor Cell 84 1996 289 297
    • (1996) Cell , vol.84 , pp. 289-297
    • Savage, B.1    Saldivar, E.2    Ruggeri, Z.M.3
  • 49
    • 0038494921 scopus 로고    scopus 로고
    • Platelet-collagen interaction: Is GPVI the central receptor?
    • B. Nieswandt, and S.P. Watson Platelet-collagen interaction: is GPVI the central receptor? Blood 102 2003 449 461
    • (2003) Blood , vol.102 , pp. 449-461
    • Nieswandt, B.1    Watson, S.P.2
  • 51
    • 0037039439 scopus 로고    scopus 로고
    • Functional self-association of von Willebrand factor during platelet adhesion under flow
    • B. Savage, J.J. Sixma, and Z.M. Ruggeri Functional self-association of von Willebrand factor during platelet adhesion under flow Proc. Natl Acad. Sci. USA 99 2002 425 430
    • (2002) Proc. Natl Acad. Sci. USA , vol.99 , pp. 425-430
    • Savage, B.1    Sixma, J.J.2    Ruggeri, Z.M.3
  • 52
  • 53
    • 19544377828 scopus 로고    scopus 로고
    • Structure and function of snake venom toxins interacting with human von Willebrand factor
    • T. Matsui, and J. Hamako Structure and function of snake venom toxins interacting with human von Willebrand factor Toxicon 45 2005 1075 1087
    • (2005) Toxicon , vol.45 , pp. 1075-1087
    • Matsui, T.1    Hamako, J.2
  • 54
    • 34247170871 scopus 로고    scopus 로고
    • The presence of active von Willebrand factor under various pathological conditions
    • E. Groot, P.G. de Groot, R. Fijnheer, and P.J. Lenting The presence of active von Willebrand factor under various pathological conditions Curr. Opin. Hematol. 14 2007 284 289
    • (2007) Curr. Opin. Hematol. , vol.14 , pp. 284-289
    • Groot, E.1    De Groot, P.G.2    Fijnheer, R.3    Lenting, P.J.4
  • 55
    • 0242266981 scopus 로고    scopus 로고
    • Shear stress and von Willebrand factor in health and disease
    • H.M. Tsai Shear stress and von Willebrand factor in health and disease Semin. Thromb. Hemost. 29 2003 479 488
    • (2003) Semin. Thromb. Hemost. , vol.29 , pp. 479-488
    • Tsai, H.M.1
  • 56
    • 0033976060 scopus 로고    scopus 로고
    • Structure and function of the von Willebrand factor A1 domain: Analysis with monoclonal antibodies reveals distinct binding sites involved in recognition of the platelet membrane glycoprotein Ib-IX-V complex and ristocetin-dependent activation
    • M. De Luca, D.A. Facey, E.J. Favaloro, M.S. Hertzberg, J.C. Whisstock, T. McNally, R.K. Andrews, and M.C. Berndt Structure and function of the von Willebrand factor A1 domain: analysis with monoclonal antibodies reveals distinct binding sites involved in recognition of the platelet membrane glycoprotein Ib-IX-V complex and ristocetin-dependent activation Blood 95 2000 164 172
    • (2000) Blood , vol.95 , pp. 164-172
    • De Luca, M.1    Facey, D.A.2    Favaloro, E.J.3    Hertzberg, M.S.4    Whisstock, J.C.5    McNally, T.6    Andrews, R.K.7    Berndt, M.C.8
  • 57
    • 14544302314 scopus 로고    scopus 로고
    • New concepts in von Willebrand disease
    • J.E. Sadler New concepts in von Willebrand disease Annu. Rev. Med. 56 2005 173 191
    • (2005) Annu. Rev. Med. , vol.56 , pp. 173-191
    • Sadler, J.E.1
  • 58
    • 77649207368 scopus 로고    scopus 로고
    • Platelet von Willebrand factor-structure, function and biological importance
    • R.T. McGrath, E. McRae, O.P. Smith, and J.S. O'Donnell Platelet von Willebrand factor-structure, function and biological importance Br J Haematol 148 2010 834 843
    • (2010) Br J Haematol , vol.148 , pp. 834-843
    • McGrath, R.T.1    McRae, E.2    Smith, O.P.3    O'Donnell, J.S.4
  • 60
    • 0037125931 scopus 로고    scopus 로고
    • Processing of von Willebrand factor by ADAMTS-13
    • D.W. Chung, and K. Fujikawa Processing of von Willebrand factor by ADAMTS-13 Biochemistry 41 2002 11065 11070
    • (2002) Biochemistry , vol.41 , pp. 11065-11070
    • Chung, D.W.1    Fujikawa, K.2
  • 61
    • 0029925856 scopus 로고    scopus 로고
    • Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis
    • M. Furlan, R. Robles, and B. Lammle Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis Blood 87 1996 4223 4234
    • (1996) Blood , vol.87 , pp. 4223-4234
    • Furlan, M.1    Robles, R.2    Lammle, B.3
  • 62
    • 4544232865 scopus 로고    scopus 로고
    • Molecular modeling of the von Willebrand factor A2 domain and the effects of associated type 2A von Willebrand disease mutations
    • DOI 10.1007/s00894-004-0194-9
    • J.J. Sutherland, L.A. O'Brien, D. Lillicrap, and D.F. Weaver Molecular modeling of the von Willebrand factor A2 Domain and the effects of associated type 2A von Willebrand disease mutations J. Mol. Model. 10 2004 259 270 (Pubitemid 39236649)
    • (2004) Journal of Molecular Modeling , vol.10 , Issue.4 , pp. 259-270
    • Sutherland, J.J.1    O'Brien, L.A.2    Lillicrap, D.3    Weaver, D.F.4
  • 63
    • 67249086879 scopus 로고    scopus 로고
    • Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor
    • Q. Zhang, Y.F. Zhou, C.Z. Zhang, X. Zhang, C. Lu, and T.A. Springer Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor Proc. Natl Acad. Sci. USA 106 2009 9226 9231
    • (2009) Proc. Natl Acad. Sci. USA , vol.106 , pp. 9226-9231
    • Zhang, Q.1    Zhou, Y.F.2    Zhang, C.Z.3    Zhang, X.4    Lu, C.5    Springer, T.A.6
  • 64
    • 0029878123 scopus 로고    scopus 로고
    • Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion
    • H.M. Tsai Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion Blood 87 1996 4235 4244
    • (1996) Blood , vol.87 , pp. 4235-4244
    • Tsai, H.M.1
  • 65
    • 66749099068 scopus 로고    scopus 로고
    • Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor
    • X. Zhang, K. Halvorsen, C.Z. Zhang, W.P. Wong, and T.A. Springer Mechanoenzymatic cleavage of the ultralarge vascular protein von Willebrand factor Science 324 2009 1330 1334
    • (2009) Science , vol.324 , pp. 1330-1334
    • Zhang, X.1    Halvorsen, K.2    Zhang, C.Z.3    Wong, W.P.4    Springer, T.A.5
  • 66
    • 58149339548 scopus 로고    scopus 로고
    • Synthesis, redox properties, and conformational analysis of vicinal disulfide ring mimics
    • E.L. Ruggles, P.B. Deker, and R.J. Hondal Synthesis, redox properties, and conformational analysis of vicinal disulfide ring mimics Tetrahedron 65 2009 1257 1267
    • (2009) Tetrahedron , vol.65 , pp. 1257-1267
    • Ruggles, E.L.1    Deker, P.B.2    Hondal, R.J.3
  • 67
  • 68
    • 0016711868 scopus 로고
    • Consideration of the possibility that the slow step in protein denaturation reactions is due to cis-trans isomerism of proline residues
    • J.F. Brandts, H.R. Halvorson, and M. Brennan Consideration of the possibility that the slow step in protein denaturation reactions is due to cis-trans isomerism of proline residues Biochemistry 14 1975 4953 4963
    • (1975) Biochemistry , vol.14 , pp. 4953-4963
    • Brandts, J.F.1    Halvorson, H.R.2    Brennan, M.3
  • 69
    • 34249071130 scopus 로고    scopus 로고
    • Force-induced prolyl cis-trans isomerization in elastin-like polypeptides
    • A. Valiaev, D.W. Lim, T.G. Oas, A. Chilkoti, and S. Zauscher Force-induced prolyl cis-trans isomerization in elastin-like polypeptides J. Am. Chem. Soc. 129 2007 6491 6497
    • (2007) J. Am. Chem. Soc. , vol.129 , pp. 6491-6497
    • Valiaev, A.1    Lim, D.W.2    Oas, T.G.3    Chilkoti, A.4    Zauscher, S.5
  • 70
    • 69249234597 scopus 로고
    • Hematologic complications arising during ristocetin therapy; Relation between dose and toxicity
    • E.J. Gangarosa, N.S. Landerman, P.J. Rosch, and E.G. Herndon Jr. Hematologic complications arising during ristocetin therapy; relation between dose and toxicity N Engl J. Med. 259 1958 156 161
    • (1958) N Engl J. Med. , vol.259 , pp. 156-161
    • Gangarosa, E.J.1    Landerman, N.S.2    Rosch, P.J.3    Herndon Jr., E.G.4
  • 71
    • 0013576562 scopus 로고
    • Ristocetin-induced thrombocytopenia: Site and mechanism of action
    • E.J. Gangarosa, T.R. Johnson, and H.S. Ramos Ristocetin-induced thrombocytopenia: site and mechanism of action Arch. Intern. Med. 105 1960 83 89
    • (1960) Arch. Intern. Med. , vol.105 , pp. 83-89
    • Gangarosa, E.J.1    Johnson, T.R.2    Ramos, H.S.3
  • 73
    • 0036108484 scopus 로고    scopus 로고
    • 3D domain swapping: As domains continue to swap
    • Y. Liu, and D. Eisenberg 3D domain swapping: as domains continue to swap Protein Sci. 11 2002 1285 1299
    • (2002) Protein Sci. , vol.11 , pp. 1285-1299
    • Liu, Y.1    Eisenberg, D.2


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.