The solution structure and dynamics of human neutrophil gelatinase-associated lipocalin
| Autor: | Coles, M, Diercks, T, Muehlenweg, B, Bartsch, S, Zolzer, V, Tschesche, Harald, Kessler, H |
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| Rok vydání: | 1999 |
| Předmět: |
Models
Molecular Neutrophils Molecular Sequence Data protein-protein interactions human neutrophil Protein Structure Secondary gelatinase-associated lipocalin Mice Lipocalin-2 Proto-Oncogene Proteins Computer Graphics Animals Humans Amino Acid Sequence Cysteine protein structure Nuclear Magnetic Resonance Biomolecular Conserved Sequence Oncogene Proteins Binding Sites Sequence Homology Amino Acid NMR Lipocalins Rats Solutions protein dynamics Carrier Proteins Sequence Alignment Acute-Phase Proteins |
| Zdroj: | Journal of molecular biology. 289(1) |
| ISSN: | 0022-2836 |
| Popis: | Human neutrophil gelatinase-associated lipocalin (HNGAL) is a member of the lipocalin family of extracellular proteins that function as transporters of small, hydrophobic molecules. HNGAL, a component of human blood granulocytes, binds bacterially derived formyl peptides that act as chemotactic agents and induce leukocyte granule discharge. HNGAL also forms a complex with the proenzyme form of matrix metalloproteinase-9 (pro-MMP-9, or progelatinase B) via an intermolecular disulphide bridge. This association allows the subsequent formation of ternary and quaternary metalloproteinase/inhibitor complexes that vary greatly in their metalloproteinase activities. The structure and dynamics of apo-HNGAL have been determined by NMR spectroscopy. Simulated annealing calculations yielded a set of 20 convergent structures with an average backbone RMSD from mean coordinate positions of 0.79(+/-0.13) Angstrom over secondary structure elements. The overall rotational correlation time (13.3 ns) derived from N-15 relaxation data is consistent with a monomeric protein of the size of HNGAL (179 residues) under the experimental conditions (1.4 mM protein, pH 6.0, 24.5 degrees C). The structure features an eight stranded antiparallel beta-barrel, typical of the lipocalin family. One end of the barrel is open, providing access to the binding site within the barrel cavity, while the other is closed by a short 3(10)-helix. The free cysteine residue required for association with pro-MMP-9 lies in an inter-strand loop at the closed end of the barrel. The structure provides a detailed model of the ligand-binding site and has led to the proposal of a site for pro-MMP-9 association. Dynamic data correlate well with structural features, which has allowed us to investigate a mechanism by which a cell-surface receptor might distinguish between apo and holo-HNGAL through conformational changes at the open end of the barrel. (C) 1999 Academic Press. |
| Databáze: | OpenAIRE |
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