X-ray structure of engineered human Aortic Preferentially Expressed Protein-1 (APEG-1)
| Autor: | Scheich Christoph, Niesen Frank H, Manjasetty Babu A, Roske Yvette, Goetz Frank, Behlke Joachim, Sievert Volker, Heinemann Udo, Büssow Konrad |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Cancer Research Protein Conformation Amino Acid Motifs Molecular Sequence Data Myocytes Smooth Muscle Biophysics Immunoglobulins Muscle Proteins Protein Serine-Threonine Kinases Crystallography X-Ray Protein Engineering Protein Structure Secondary Cell Adhesion Escherichia coli Humans Amino Acid Sequence Cloning Molecular Databases Protein Protein Structure Quaternary lcsh:QH301-705.5 Sequence Homology Amino Acid Lysine Arteries Protein Structure Tertiary Kinetics lcsh:Biology (General) Dimerization Oligopeptides Ultracentrifugation Research Article Protein Binding |
| Zdroj: | BMC Structural Biology BMC Structural Biology, Vol 5, Iss 1, p 21 (2005) |
| ISSN: | 1472-6807 |
| Popis: | Background Human Aortic Preferentially Expressed Protein-1 (APEG-1) is a novel specific smooth muscle differentiation marker thought to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). Results Good quality crystals that were suitable for X-ray crystallographic studies were obtained following the truncation of the 14 N-terminal amino acids of APEG-1, a region predicted to be disordered. The truncated protein (termed ΔAPEG-1) consists of a single immunoglobulin (Ig) like domain which includes an Arg-Gly-Asp (RGD) adhesion recognition motif. The RGD motif is crucial for the interaction of extracellular proteins and plays a role in cell adhesion. The X-ray structure of ΔAPEG-1 was determined and was refined to sub-atomic resolution (0.96 Å). This is the best resolution for an immunoglobulin domain structure so far. The structure adopts a Greek-key β-sandwich fold and belongs to the I (intermediate) set of the immunoglobulin superfamily. The residues lying between the β-sheets form a hydrophobic core. The RGD motif folds into a 310 helix that is involved in the formation of a homodimer in the crystal which is mainly stabilized by salt bridges. Analytical ultracentrifugation studies revealed a moderate dissociation constant of 20 μM at physiological ionic strength, suggesting that APEG-1 dimerisation is only transient in the cell. The binding constant is strongly dependent on ionic strength. Conclusion Our data suggests that the RGD motif might play a role not only in the adhesion of extracellular proteins but also in intracellular protein-protein interactions. However, it remains to be established whether the rather weak dimerisation of APEG-1 involving this motif is physiogically relevant. |
| Databáze: | OpenAIRE |
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