The col-1 module of human matrix metalloproteinase-2 (MMP-2): Structural/functional relatedness between gelatin-binding fibronectin type II modules and lysine-binding kringle domains

Marion Gehrmann, Klára Briknarová, L. Bányai, L. Patthy, Miguel Llinás

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Abstract

Human matrix metalloproteinase-2 (MMP-2) contains three in-tandem fibronectin type II (FII) repeats that bind gelatin. Here, we report the NMR solution structure of the first FII module of MMP-2 (col-1). The latter is described as a characteristic, globular FII fold containing two β-sheets, a stretch of 31-helix, a turn of α-helix, and an exposed hydrophobic surface lined with aromatic residues. We show that col-1 binds (Pro-Pro-Gly)6, a mimic of gelatin, with a Ka of approx. 0.42 mm-1, and that its binding site involves a number of aromatic residues as well as Arg34, as previously found for the second and third homologous repeats. Moreover, the affinity of the in-tandem col-1+2 construct (col-12) toward the longer ligand (Pro-Pro-Gly)12 is twice that for (Pro-Pro-Gly)6, as expected from mass action. A detailed structural comparison between FII and kringle domains indicates that four main conformational features are shared: two antiparallel β-sheets, a central 31-helix, and the quasi-perpendicular orientation of the two proximal Cys-Cys bonds. Structure superposition by optimizing overlap of cystine bridge areas results in close juxta-position of their main β-sheets and 31-helices, and reveals that the gelatin binding site of FII modules falls at similar locations and exhibits almost identical topological features to those of the lysine binding site of kringle domains. Thus, despite the minor (

Original languageEnglish
Pages (from-to)137-148
Number of pages12
JournalBiological Chemistry
Volume383
Issue number1
DOIs
Publication statusPublished - 2002

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Kringles
prolyl-prolyl-glycine
Gelatin
Fibronectins
Lysine
Binding Sites
cysteinylcysteine
Cystine
Matrix Metalloproteinase 2
Nuclear magnetic resonance
human MMP2 protein
Ligands
poly(prolylprolylglycine)15

ASJC Scopus subject areas

  • Biochemistry

Cite this

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abstract = "Human matrix metalloproteinase-2 (MMP-2) contains three in-tandem fibronectin type II (FII) repeats that bind gelatin. Here, we report the NMR solution structure of the first FII module of MMP-2 (col-1). The latter is described as a characteristic, globular FII fold containing two β-sheets, a stretch of 31-helix, a turn of α-helix, and an exposed hydrophobic surface lined with aromatic residues. We show that col-1 binds (Pro-Pro-Gly)6, a mimic of gelatin, with a Ka of approx. 0.42 mm-1, and that its binding site involves a number of aromatic residues as well as Arg34, as previously found for the second and third homologous repeats. Moreover, the affinity of the in-tandem col-1+2 construct (col-12) toward the longer ligand (Pro-Pro-Gly)12 is twice that for (Pro-Pro-Gly)6, as expected from mass action. A detailed structural comparison between FII and kringle domains indicates that four main conformational features are shared: two antiparallel β-sheets, a central 31-helix, and the quasi-perpendicular orientation of the two proximal Cys-Cys bonds. Structure superposition by optimizing overlap of cystine bridge areas results in close juxta-position of their main β-sheets and 31-helices, and reveals that the gelatin binding site of FII modules falls at similar locations and exhibits almost identical topological features to those of the lysine binding site of kringle domains. Thus, despite the minor (",
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T1 - The col-1 module of human matrix metalloproteinase-2 (MMP-2)

T2 - Structural/functional relatedness between gelatin-binding fibronectin type II modules and lysine-binding kringle domains

AU - Gehrmann, Marion

AU - Briknarová, Klára

AU - Bányai, L.

AU - Patthy, L.

AU - Llinás, Miguel

PY - 2002

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N2 - Human matrix metalloproteinase-2 (MMP-2) contains three in-tandem fibronectin type II (FII) repeats that bind gelatin. Here, we report the NMR solution structure of the first FII module of MMP-2 (col-1). The latter is described as a characteristic, globular FII fold containing two β-sheets, a stretch of 31-helix, a turn of α-helix, and an exposed hydrophobic surface lined with aromatic residues. We show that col-1 binds (Pro-Pro-Gly)6, a mimic of gelatin, with a Ka of approx. 0.42 mm-1, and that its binding site involves a number of aromatic residues as well as Arg34, as previously found for the second and third homologous repeats. Moreover, the affinity of the in-tandem col-1+2 construct (col-12) toward the longer ligand (Pro-Pro-Gly)12 is twice that for (Pro-Pro-Gly)6, as expected from mass action. A detailed structural comparison between FII and kringle domains indicates that four main conformational features are shared: two antiparallel β-sheets, a central 31-helix, and the quasi-perpendicular orientation of the two proximal Cys-Cys bonds. Structure superposition by optimizing overlap of cystine bridge areas results in close juxta-position of their main β-sheets and 31-helices, and reveals that the gelatin binding site of FII modules falls at similar locations and exhibits almost identical topological features to those of the lysine binding site of kringle domains. Thus, despite the minor (

AB - Human matrix metalloproteinase-2 (MMP-2) contains three in-tandem fibronectin type II (FII) repeats that bind gelatin. Here, we report the NMR solution structure of the first FII module of MMP-2 (col-1). The latter is described as a characteristic, globular FII fold containing two β-sheets, a stretch of 31-helix, a turn of α-helix, and an exposed hydrophobic surface lined with aromatic residues. We show that col-1 binds (Pro-Pro-Gly)6, a mimic of gelatin, with a Ka of approx. 0.42 mm-1, and that its binding site involves a number of aromatic residues as well as Arg34, as previously found for the second and third homologous repeats. Moreover, the affinity of the in-tandem col-1+2 construct (col-12) toward the longer ligand (Pro-Pro-Gly)12 is twice that for (Pro-Pro-Gly)6, as expected from mass action. A detailed structural comparison between FII and kringle domains indicates that four main conformational features are shared: two antiparallel β-sheets, a central 31-helix, and the quasi-perpendicular orientation of the two proximal Cys-Cys bonds. Structure superposition by optimizing overlap of cystine bridge areas results in close juxta-position of their main β-sheets and 31-helices, and reveals that the gelatin binding site of FII modules falls at similar locations and exhibits almost identical topological features to those of the lysine binding site of kringle domains. Thus, despite the minor (

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