A Caltech Library Service

Expression and crystallization of a soluble and functional form of an Fc receptor related to class I histocompatibility molecules

Gastinel, Louis N. and Simister, Neil E. and Bjorkman, Pamela J. (1992) Expression and crystallization of a soluble and functional form of an Fc receptor related to class I histocompatibility molecules. Proceedings of the National Academy of Sciences of the United States of America, 89 (2). pp. 638-642. ISSN 0027-8424. PMCID PMC48294. doi:10.1073/pnas.89.2.638.

PDF - Published Version
See Usage Policy.


Use this Persistent URL to link to this item:


Maternal transport of immunoglobulin to the newborn mammal is important for immune defense during the first weeks of independent life. Receptors for the Fc portion of IgG mediate the transfer of immunoglobulin from milk to the bloodstream of newborn mice and rats, by passage through intestinal epithelial cells. Neonatal Fc receptors (FcRn) isolated from intestinal epithelial cells of suckling rats bear a striking resemblance to class I histocompatibility molecules. The heavy chain of FcRn has sequence similarity in three extracellular domains to the corresponding domains of class I molecules, and the light chain of both types of molecules is β_2-microglobulin. To facilitate biochemical characterization and crystallization of FcRn, we have expressed a secreted form, as well as two different lipid-linked forms solubilizable by phospholipase treatment. The lipid-linked forms are heterodimers consisting of β_2-microglobulin and the extracellular portion of the heavy chain and are anchored to the membrane by a phosphatidylinositol linkage attached to either the heavy chain or β_2-microglobulin. Cells expressing either lipid-linked form bind rat Fc, reproducing the known physiological pH dependence of binding. Secreted FcRn has been purified in yields up to 40 mg/liter from cell supernatants. Circular dichroism spectra of soluble FcRn appear similar to spectra of class I MHC molecules, suggesting that the similarities in primary sequence extend also to a similarity in secondary structure. Soluble FcRn crystallizes in a form amenable to a structure determination by x-ray diffraction methods, which will ultimately allow a detailed comparison of the two types of molecules.

Item Type:Article
Related URLs:
URLURL TypeDescription DOIArticle CentralArticle
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 1992 National Academy of Sciences. Communicated by Don C. Wiley, October 25, 1991 (received for review September 17, 1991). We thank Drs. Lennart Lddgberg for the anti-rat β2m monoclonal antibody, Don Wiley and Anastasia Haykov for HLA-B40, Chris Bebbington for the glutamine synthetase vector, Alan Waring and Ilana Tamir for analysis of CD spectra, and Rochelle Diamond for help with flow cytometry. We thank Roland Strong and David Penny for help with crystallization and tissue culture. This work was supported by the National Institutes of Health (AI28931 to P.J.B. and HD27691 to N.E.S.) and the Centre National de la Recherche Scientifique (L.N.G.). P.J.B. is a Pew scholar and has a Young Investigator Award from the Cancer Research Institute. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Funding AgencyGrant Number
Centre National de la Recherche Scientifique (CNRS)UNSPECIFIED
Cancer Research InstituteUNSPECIFIED
Subject Keywords:immunoglobulin receptor; protein engineering; amplifiable expression system; circular dichroism
Issue or Number:2
PubMed Central ID:PMC48294
Record Number:CaltechAUTHORS:20141215-153014968
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52829
Deposited By: Tony Diaz
Deposited On:15 Dec 2014 23:40
Last Modified:10 Nov 2021 19:44

Repository Staff Only: item control page