Determination of the Crystal Structure of Human Zn-Alpha 2-Gylcoprotein, A Protein Implicated in Breast Cancer
Abstract
Zn-alpha 2-glycoprotein (ZAG) is a 41 kDa soluble protein whose sequence and domain organization are surprisingly similar to those of the membrane glycoproteins of the major histocompatibility complex (MHC). MHC molecules function in the presentation of peptide antigens to cytotoxic T cells during immune surveillance, but recent data indicate that ZAG stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. In addition, ZAG is found in high concentrations in 40% of mammary carcinomas, as well as in cysts from breast gross cystic disease. These data suggest that ZAG participates in the development of breast diseases including breast carcinomas. We purified ZAG from human serum and solved the crystal structure to 2.8 A resolution. ZAG resembles a class I major histocompatibility complex heavy chain, but ZAG does not bind the class I light chain beta 2-microglobulin. The ZAG counterpart of the MHC peptide binding groove contains electron density corresponding to a hydrophobic, non- peptidic compound that may be implicated in lipid catabolism under normal or pathological conditions. We have initiated mass spectrometry assays to identify the ligand and are testing the ability of hydrophobic small molecules to bind to serum-derived ZAG and to ZAG produced in bacteria, which presumably does not contain a hydrophobic ligand.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2000
- Accession Number
- ADA386587
Entities
People
- Arthur Chirino
- Pamela Bjorkman
Organizations
- California Institute of Technology