Oncostatin M (OM)
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| OM Homology Model Based on NMR Data structure published in: Biochemistry (1998), 37(30) 10581-10588. |
| OM X-ray Structure
PDB ID: 1EVS, M. C. Deller et al. (2000) Structure 8:863 |
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Oncostatin M (OM) is a member of cytokine family which regulates the proliferation and differentiation of a variety of cell types and includes interleukin-4 (IL-4), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and granulocyte-colony stimulating factor (G-CSF). This family of proteins adopt a four helix bundle fold with up-up-down-down topology and contain intramolecular disulfide bonds. The shared functions of these proteins are mediated through the interaction of the signal transducing membrane glycoprotein, gp130, with the extracellular domains of these cytokine receptors. Additional biological activities attributed to OM include the inhibition of several tumor cell lines, inhibition of embryonic stem cell differentiation a regulator of endothelial cells and the growth stimulation of several fibroblast cell lines. OM has also been shown to be a mitogen for AIDS-related Kaposi's sarcoma cells, where it functions as an autocrine growth factor.
Since an X-ray or NMR structure for OM is not currently available, a homology model for OM was determined from the X-ray structures of hGH, LIF and G-CSF where the alignment was based on the NMR secondary structure instead of sequence. The OM secondary structure was determined from NMR structural data and the secondary structure for hGH, LIF and G-CSF were obtained from the reported X-ray structures. The resulting homology model was refined using sequential NOE distance restraints, 13C chemical shift information and a conformational database.
The typical approach to homology modeling has relied heavily on sequence similarity between the new protein and target protein(s). The accuracy of the resulting homology model decreases significantly as the sequence homology between the structures drops below 40%. This is clearly problematic since a number of protein families have very divergent sequence homology (20% or less) while maintaining the same overall fold. Attempts have been made to use predictive methods to identify regions of secondary structure to generate alignments for homology modeling, but this approach is lacking since the validity of the resulting structure is dependent on both the combined accuracy of the structure prediction method and the homology modeling protocol. Nevertheless, the concept of using secondary structure alignment instead of sequence alignment to thread a homology model represents a better approach because of the higher information content.
See also the IL-13 and IL-4 web pages.