Crystal structures of NK1-heparin complexes reveal the basis for NK1 activity and enable engineering of potent agonists of the MET receptor

EMBO Journal

Volumn 20, Issue 20, 2001, Pages 5543-5555

  Lietha, Daniel ^a   Chirgadze, Dimitri Y ^b   Mulloy, Barbara ^c   Blundell, Tom L ^b   Gherardi, Ermanno ^a  

^a MEDICAL RESEARCH COUNCIL   (United Kingdom)

^b UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^c NATIONAL INSTITUTE FOR BIOLOGICAL STANDARDS AND CONTROL   (United Kingdom)

Author keywords

Heparan sulfate; Hepatocyte growth factor; MET; NK1; Protein engineering; Scatter factor

Indexed keywords

HEPARAN SULFATE; HEPARIN; PROTEIN NK1; SCATTER FACTOR; SCATTER FACTOR RECEPTOR AGONIST; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; BINDING SITE; CRYSTAL STRUCTURE; DRUG MECHANISM; DRUG STRUCTURE; GENETIC ENGINEERING; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; X RAY ANALYSIS;

ANIMALS; BINDING SITES; CELL LINE; CRYSTALLOGRAPHY, X-RAY; DIMERIZATION; DOGS; DRUG DESIGN; HEPARIN; HEPARITIN SULFATE; HEPATOCYTE GROWTH FACTOR; HUMANS; KIDNEY; KRINGLES; MACROMOLECULAR SUBSTANCES; MODELS, MOLECULAR; MUTAGENESIS, SITE-DIRECTED; PEPTIDE FRAGMENTS; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; PROTO-ONCOGENE PROTEINS C-MET; RECOMBINANT FUSION PROTEINS; RNA SPLICING; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0035887033     PISSN: 02614189     EISSN: None     Source Type: Journal    
DOI: 10.1093/emboj/20.20.5543     Document Type: Article

References (64)

1. Crystalline structure of heparin
2. 3D domain swapping: A mechanism for oligomer assembly
3. Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud
4. Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product
5. Crystallography and NMR system (CNS): A new determination
6. Renal agenesis in mice homozygous for a gene trap mutation in the gene encoding heparan sulfate 2-sulfotransferase
7. The branchial arches and HGF are growth-promoting and chemoattractant for cranial motor axons
8. Identification of a competitive HGF antagonist encoded by an alternative transcript
9. Crystal structure of the NK1 fragment of HGF/SF suggests a novel mode for growth factor dimerization and receptor binding
10. Hepatocyte growth factor (HGF)/NK1 is a naturally occurring HGF/scatter factor variant with partial agonist/antagonist activity
11. The CCP4 suite: Programs for protein crystallography
12. Structure of a heparin-linked biologically active dimer of fibroblast growth factor
13. Molecular evolution and domain structure of plasminogen-related growth factors (HGF/SF and HGF1/MSP)
14. Hepatocyte growth factor/scatter factor is an axonal chemoattractant and a neurotrophic factor for spinal motor neurons
15. An extensively modified version of MolScript that includes greatly enhanced coloring capabilities
16. Heparin structure and interactions with basic fibroblast growth factor
17. Evidence for non-covalent clusters of the c-met proto-oncogene product
18. Purification of scatter factor, a fibroblast-derived basic protein that modulates epithelial interactions and movement
19. Structure of a heparan sulphate oligosaccharide that binds to basic fibroblast growth factor
20. A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis
21. Engineered mutants of HGF/SF with reduced binding to heparan sulphate proteoglycans, decreased clearance and enhanced activity in vivo [published erratum appears in Curr. Biol., 1998, 8, R739]
22. 'Diabodies': Small bivalent and bispecific antibody fragments
23. NK1, a natural splice variant of hepatocyte growth factor/scatter factor, is a partial agonist in vivo
24. Hepatocyte growth factor/scatter factor - Met signaling in tumorigenicity and invasion/metastasis
25. Improved methods for binding protein models in electron density maps and the location of errors in these models
26. Efficient rebuilding of protein structures
27. MOLSCRIPT: A program to produce both detailed and schematic plots of protein structures
28. PROCHECK: A program to check the stereochemical quality of protein structures
29. Generation and characterization of a competitive antagonist of human hepatocyte growth factor, HGF/NK1
30. Interaction of hepatocyte growth factor with heparan sulfate. Elucidation of the major heparan sulfate structural determinants
31. Activation of hepatocyte growth factor by the plasminogen activators uPA and tPA
32. Solvent content of protein crystals
33. RASTER 3D version 2.0, a program for photorealistic molecular graphics
34. Molecular cloning and sequence analysis of cDNA for human hepatocyte growth factor
35. An alternatively processed mRNA generated from human hepatocyte growth factor gene
36. Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII
37. Hairpin loop and second kringle domain are essential sites for heparin binding and biological activity of hepatocyte growth factor
38. HGF/SF inhibits junctional communication
39. Conformation and dynamics of heparin and heparan sulfate
40. Molecular cloning and expression of human hepatocyte growth factor
41. Extracellular proteolytic cleavage by urokinase is required for activation of hepatocyte growth factor/scatter factor
42. AMoRe: An automated package for molecular replacement
43. Protein folding and association: Insights from the interfacial and thermodynamic properties of hydrocarbons
44. Processing of X-ray diffraction data collected in the oscillation mode
45. Cell surface heparan sulfate proteoglycans: Selective regulators of ligand-receptor encounters
46. Crystal structure of fibroblast growth factor receptor ectodomain bound to ligand and heparin
47. Crystal structure of a diabody, a bivalent antibody fragment
48. Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation
49. Defective heparan sulfate biosynthesis and neonatal lethality in mice lacking N-deacetylase/N-sulfotransferase-1
50. Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex
51. Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization
52. Scatter factor/hepatocyte growth factor is essential for liver development
53. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas
54. Heparin induces dimerization and confers proliferative activity onto the hepatocyte growth factor antagonists NK1 and NK2
55. Activation of hepatocyte growth factor by two homologous proteases, blood-coagulation factor XIIa and hepatocyte growth factor activator
56. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility
57. Identification of the basic fibroblast growth factor binding sequence in fibroblast heparan sulfate
58. Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor
59. Crystal structure of the NK1 fragment of human hepatocyte growth factor at 2.0 Å resolution
60. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor
61. Frequency of TPR-MET rearrangement in patients with gastric carcinoma and in first-degree relatives
62. Crystal structure of human stem cell factor: Implication for stem cell factor receptor dimerization and activation
63. The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site
64. Identification and dynamics of a heparin-binding site in hepatocyte growth factor