title: Transient collagen triple helix binding to a key metalloproteinase in invasion and development.
abstract: Skeletal development and invasion by tumor cells depends on proteolysis of collagen by the pericellular metalloproteinase MT1-MMP. Its hemopexin-like (HPX) domain binds to collagen substrates to facilitate their digestion. Spin labeling and paramagnetic nuclear magnetic resonance (NMR) detection have revealed how the HPX domain docks to collagen I-derived triple helix. Mutations impairing triple-helical peptidase activity corroborate the interface. Saturation transfer difference NMR suggests rotational averaging around the longitudinal axis of the triple-helical peptide. Part of the interface emerges as unique and potentially targetable for selective inhibition. The triple helix crosses the junction of blades I and II at a 45° angle to the symmetry axis of the HPX domain, placing the scissile Gly∼Ile bond near the HPX domain and shifted ∼25 Å from MMP-1 complexes. This raises the question of the MT1-MMP catalytic domain folding over the triple helix during catalysis, a possibility accommodated by the flexibility between domains suggested by atomic force microscopy images.
authors: Department of Biochemistry, University of Missouri, 117 Schweitzer Hall, Columbia, MO 65211, USA.
authors: Yingchu
authors: Y
authors: Zhao
authors: Department of Biochemistry, University of Missouri, 117 Schweitzer Hall, Columbia, MO 65211, USA.
authors: Thomas C
authors: TC
authors: Marcink
authors: Department of Physics and Astronomy, University of Missouri, Columbia, MO 65211, USA.
authors: Raghavendar Reddy
authors: RR
authors: Sanganna Gari
authors: Department of Physics and Astronomy, University of Missouri, Columbia, MO 65211, USA.
authors: Brendan P
authors: BP
authors: Marsh
authors: Department of Biochemistry, University of Missouri, 117 Schweitzer Hall, Columbia, MO 65211, USA; Department of Physics and Astronomy, University of Missouri, Columbia, MO 65211, USA.
authors: Gavin M
authors: GM
authors: King
authors: Torrey Pines Institute for Molecular Studies, 11350 Southwest Village Parkway, Port Saint Lucie, FL 34987, USA.
authors: Roma
authors: R
authors: Stawikowska
authors: Torrey Pines Institute for Molecular Studies, 11350 Southwest Village Parkway, Port Saint Lucie, FL 34987, USA.
authors: Gregg B
authors: GB
authors: Fields
authors: Department of Biochemistry, University of Missouri, 117 Schweitzer Hall, Columbia, MO 65211, USA. Electronic address: vandorens@missouri.edu.
authors: Steven R
authors: SR
authors: Van Doren
mesh_terms: D000595:Amino Acid Sequence; D003094:Collagen / Q000737:chemistry* / Q000378:metabolism*; D003461:Crystallography; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D053511:Matrix Metalloproteinase 14 / Q000737:chemistry* / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D011485:Protein Binding; D011487:Protein Conformation; D059748:Proteolysis; D013113:Spin Labels
chemical_list: D013113:Spin Labels; D003094:Collagen; D053511:Matrix Metalloproteinase 14
references: J Biol Chem. 2011 Dec 30;286(52):45073-82
references: 22030392
references: Blood. 2009 Jul 9;114(2):237-47
references: 19339693
references: PLoS One. 2011;6(9):e24029
references: 21912660
references: J Biol Chem. 2013 Oct 18;288(42):30659-71
references: 24025334
references: Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1656-66
references: 21666120
references: Cancer Res. 2012 May 1;72(9):2339-49
references: 22406620
references: J Biol Chem. 2002 Mar 8;277(10):8440-8
references: 11779859
references: J Cell Biol. 2004 Nov 22;167(4):769-81
references: 15557125
references: EMBO J. 1994 Mar 15;13(6):1263-9
references: 8137810
references: J Cell Biol. 2004 Nov 22;167(4):757-67
references: 15545316
references: Org Biomol Chem. 2010 Mar 21;8(6):1237-58
references: 20204190
references: Mol Biol Cell. 2014 Sep 1;25(17):2556-70
references: 24989798
references: Bioinformatics. 2013 Apr 1;29(7):845-54
references: 23407358
references: J Biol Chem. 2011 Oct 28;286(43):37535-42
references: 21896477
references: Int J Biochem Cell Biol. 2012 Feb;44(2):393-403
references: 22138224
references: J Am Chem Soc. 2012 Feb 1;134(4):2100-10
references: 22239621
references: Mol Biol Cell. 2006 Dec;17(12):5390-9
references: 17050733
references: Cell. 2003 Jul 11;114(1):33-45
references: 12859896
references: EMBO J. 2001 Sep 3;20(17):4782-93
references: 11532942
references: Cell. 1999 Oct 1;99(1):81-92
references: 10520996
references: Anal Biochem. 2007 Dec 1;371(1):43-51
references: 17706587
references: Chem Rev. 2009 Sep;109(9):4108-39
references: 19522502
references: J Biol Chem. 2009 Sep 4;284(36):24017-24
references: 19574232
references: J Biol Chem. 2001 Jul 13;276(28):25705-14
references: 11335709
references: Anal Biochem. 2004 May 15;328(2):166-73
references: 15113693
references: Biochem J. 2011 Dec 15;440(3):319-26
references: 21846327
references: J Biol Chem. 2004 Oct 8;279(41):43336-44
references: 15292230
references: Structure. 1995 Jun 15;3(6):527-30
references: 8590012
references: Biochemistry. 2007 Mar 27;46(12):3724-33
references: 17338550
references: J Biol Chem. 2004 Dec 3;279(49):51148-55
references: 15381707
references: Circulation. 2008 Feb 19;117(7):931-9
references: 18250269
references: Nat Struct Biol. 1995 Nov;2(11):938-42
references: 7583664
references: J Biol Chem. 1997 Jan 24;272(4):2446-51
references: 8999957
references: J Magn Reson. 2010 Mar;203(1):190-8
references: 20031460
references: Proteins. 2007 Dec 1;69(4):726-33
references: 17803234
references: Mol Biol Cell. 2008 Aug;19(8):3221-33
references: 18495869
references: Arterioscler Thromb Vasc Biol. 2008 Sep;28(9):1647-53
references: 18566294
references: Biochemistry. 2000 May 9;39(18):5355-65
references: 10820006
references: Structure. 2007 Oct;15(10):1159-61
references: 17937904
references: J Biol Chem. 2008 May 9;283(19):13053-62
references: 18337248
references: J Am Chem Soc. 2008 Jun 4;130(22):7011-21
references: 18465858
references: J Biol Chem. 2011 Mar 4;286(9):7587-600
references: 21193411
references: Chem Commun (Camb). 2012 Jan 21;48(6):811-3
references: 22143456
references: J Biol Chem. 2013 Dec 6;288(49):35126-37
references: 24165131
references: Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12461-6
references: 22761315
references: Arthritis Rheum. 2009 Mar;60(3):686-97
references: 19248098
references: J Biol Chem. 2000 Dec 15;275(50):39497-506
references: 10991943
references: J Am Chem Soc. 2003 Feb 19;125(7):1731-7
references: 12580598
references: J Biol Chem. 2001 Oct 5;276(40):37491-500
references: 11448964
references: J Cell Sci. 2005 Jan 1;118(Pt 1):147-56
references: 15601659
references: ACS Chem Biol. 2014 Apr 18;9(4):957-66
references: 24495220