1998 Fiscal Year Final Research Report Summary
Study of biomolecular complex formation by heteronuclear multidimensional NMR
| Project/Area Number |
09307054
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
医薬分子機能学
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
KOBAYASHI Yuji Graduate sxhool of pharmaceutical sciences, Osaka university, Professor, 薬学研究科, 教授 (20127228)
|
|---|
| Project Period (FY) |
1997 – 1998
|
| Keywords | complex / BMP / receptor / NMR / tertiary structure |
|---|
| Research Abstract |
Many biomolecules form non-covalent complexes (super molecules) when they are biologically active. In the case of molecules that act in signaling systems, the formation of the non-covalent complex is the initial event that triggers some important biological process. Although many studies have been made on such complexes, little is known about the detailed mechanism of signaling. The purpose of this research project is to explore the structure and dynamics of such protein-protein complexes by multidimensional NMR techniques. Moreover, we also intend to develop physico-chemical methodologies, which are based on sedimentation equilibrium measurements, differential scanning calorimetry and surface plasmon resonance, to investigate the mechanism of complex formation. In particular, we are focusing our attention on the BMP(bone morphogenetic protein) system. We have established a bacterial expression system for BMP and its receptor molecules. The purified recombinant BMP receptor showed high binding affinity, which was analyzed quantitatively by several physico- chemical methods. Site directed mutagenesis studies have revealed that certain amino acid residues of the BMP receptor contribute to complex formation. Using heteronuclear multidimensional NMR methods, the assignments of the BMP receptor are complete and the solution structure of BMP receptor nearly determined. In other words, we have powerful tools and methods to investigate the BMP-BMP receptor complex at high (atomic) resolution.
|
