Determination of the Crystal Structure of Human Zn-Alpha 2-Glycoprotein, A Protein Implicated in Breast Cancer
Annual rept. 1 Aug 97-31 Jul 98
CALIFORNIA INST OF TECH PASADENA
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Zn-alpha-2-glycoprotein ZAG is a soluble protein related to class I major histocompatibility complex MHC proteins. ZAG is present in most bodily fluids. In addition, ZAG accumulates in breast cysts as well as in 40 of breast carcinomas. ZAG stimulates lipid degradation in adipocytes and appears to be responsible of the massive loss of fat tissue happening in some patients with advanced cancer. We have solved the three-dimensional structure of human ZAG. ZAG is strikingly similar to class I MHC proteins but it does not bind Beta-2-microglobulin. A network of hydrogen bonds between ZAGs first domains and the last one stabilizes ZAG in the absence of Beta-2-microglobulin. ZAG carries a hydrophobic non-peptidic ligand in the homologous site to the peptide binding groove of other MHC molecules. We are studying the identity and role of this ligand in ZAGs function.
- Medicine and Medical Research