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Biochemical characterization and crystalization of human Zn-α2-glycoprotein, a soluble class I major histocompatibility complex homolog

Sánchez, Luis M. and López-Otín, Carlos and Bjorkman, Pamela J. (1997) Biochemical characterization and crystalization of human Zn-α2-glycoprotein, a soluble class I major histocompatibility complex homolog. Proceedings of the National Academy of Sciences of the United States of America, 94 (9). pp. 4626-4630. ISSN 0027-8424. PMCID PMC20774. https://resolver.caltech.edu/CaltechAUTHORS:20141203-095910857

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Abstract

Zn-α2-glycoprotein (ZAG) is a 41-kDa soluble protein that is present in most bodily fluids. In addition, ZAG accumulates in fluids from breast cysts and in 40% of breast carcinomas, which suggests that ZAG plays a role in the development of breast diseases. However, the function of ZAG under physiological and cancerous conditions remains unknown. Because ZAG shares 30–40% sequence identity with the heavy chains of class I major histocompatibility complex (MHC) proteins, we compared the biochemical properties of ZAG with those of classical class I MHC molecules. We purified human ZAG from breast cyst fluid and serum and produced a panel of anti-ZAG monoclonal antibodies. Binding assays and acid elution experiments revealed that, in contrast to class I MHC proteins, ZAG does not bind peptides or the class I light chain, β2-microglobulin (β_(2)m). Nevertheless, CD studies indicated that ZAG is thermally stable in the absence of bound peptide or associated β2m, as opposed to class I MHC molecules, which require the presence of both β2m and peptides for stability. These data indicate that the function of ZAG has diverged from the peptide presentation and T-cell interaction functions of class I molecules. To gain insight into the function of ZAG and to compare the three-dimensional structures of ZAG and class I MHC molecules, we produced ZAG crystals that diffract beyond 2.7 Å and have initiated an x-ray structure determination.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.94.9.4626DOIArticle
http://www.pnas.org/content/94/9/4626PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20774/PubMed CentralArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 1997 The National Academy of Sciences. Received December 16, 1996; accepted February 21, 1997. We thank Dr. F. Vizoso for breast cyst fluid, Dr. S. Mayo and his laboratory for use of the CD spectrometer, Dr. M. Harrington for use of the PhastSystem, S. Ou and the Caltech monoclonal antibody facility, Dr. Gary Hathaway and the Caltech PPMAL facility, and Dr. A. Chirino for data collection and processing at Cornell High Energy Synchrotron Source. L.M.S. was supported by the Fulbright Visiting Scholar Program.
Funders:
Funding AgencyGrant Number
Fulbright FoundationUNSPECIFIED
Issue or Number:9
PubMed Central ID:PMC20774
Record Number:CaltechAUTHORS:20141203-095910857
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141203-095910857
Official Citation:Sánchez, L. M., López-Otín, C., & Bjorkman, P. J. (1997). Biochemical characterization and crystalization of human Zn-α2-glycoprotein, a soluble class I major histocompatibility complex homolog. Proceedings of the National Academy of Sciences, 94(9), 4626-4630.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52316
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:03 Dec 2014 21:55
Last Modified:03 Oct 2019 07:41

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