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X-ray structure of engineered human Aortic Preferentially Expressed Protein-1 (APEG-1)

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Item Type:Article
Title:X-ray structure of engineered human Aortic Preferentially Expressed Protein-1 (APEG-1)
Creators Name:Manjasetty, B.A. and Niesen, F.H. and Scheich, C. and Roske, Y. and Goetz, F. and Behlke, J. and Sievert, V. and Heinemann, U. and Buessow, K.
Abstract: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 DeltaAPEG-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 DeltaAPEG-1 was determined and was refined to sub-atomic resolution (0.96 A). This is the best resolution for an immunoglobulin domain structure so far. The structure adopts a Greek-key beta-sandwich fold and belongs to the I (intermediate) set of the immunoglobulin superfamily. The residues lying between the beta-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 microM 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 physiologically relevant.
Keywords:Amino Acid Motifs, Amino Acid Sequence, Arteries, Biophysics, Cell Adhesion, Molecular Cloning, X-Ray Crystallography, Protein Databases, Dimerization, Escherichia ColiImmunoglobulins, Kinetics, Lysine, Molecular Models, Molecular Sequence Data, Muscle Proteins, Smooth Muscle Myocytes
Source:BMC Structural Biology
ISSN:1472-6807
Publisher:BioMed Central (U.K.)
Volume:5
Number:14
Page Range:21
Date:14 December 2005
Official Publication:https://doi.org/10.1186/1472-6807-5-21
PubMed:View item in PubMed

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