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Stability of empty and peptide-loaded class II major histocompatibility complex molecules at neutral and endosomal pH: Comparison to class I proteins

Reich, Ziv and Altman, John D. and Boniface, J. Jay and Lyons, Daniel S. and Kozono, Haruo and Ogg, Graham and Morgan, Chantal S. and Davis, Mark M. (1997) Stability of empty and peptide-loaded class II major histocompatibility complex molecules at neutral and endosomal pH: Comparison to class I proteins. Proceedings of the National Academy of Sciences of the United States of America, 94 (6). pp. 2495-2500. ISSN 0027-8424. PMCID PMC20116. https://resolver.caltech.edu/CaltechAUTHORS:20141203-100719213

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Abstract

The structure and thermal stability of empty and peptide-filled forms of the murine class II major histocompatibility complex (MHC) molecule I-E^k were studied at neutral and mildly acidic pH. The two forms have distinct circular dichroic spectra, suggesting that a conformational change may accompany peptide binding. Thermal stability profiles indicate that binding of peptide significantly increases the thermal stability of the empty heterodimers at both neutral and mildly acidic pH. Free energies calculated from these data provide a direct measure of this stabilization and show that the empty form of I-E^k is significantly more stable than that of class I MHC proteins. Furthermore, for the two MHC class II proteins that were analyzed (I-E^k and I-A^d), thermal stability was not significantly altered by acidification. In contrast, of four class I MHC molecules studied, three have shown a significant loss in complex stability at low pH. The marked stability exhibited by their empty form, as well as their resistance to low pH, as observed in this study, correlate well with the ability of class II MHC molecules to traverse and bind peptides in acidic endosomal vesicles.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.94.6.2495DOIArticle
http://www.pnas.org/content/94/6/2495PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC20116/PubMed CentralArticle
Additional Information:© 1997 The National Academy of Sciences. Accepted December 30, 1996. We thank Jack Aviv and his colleagues in Aviv Associates (Lakewood, NJ) for the use of the 62A DS spectropolarimeter and for their helpful advice and assistance and Dr. Harden McConnell for critical reading of the manuscript. HLA-B27 used in this study was a generous gift from José A. Lebron and Pamela J. Bjorkman. Z.R. was supported by a postdoctoral fellowship from the Rothschild Foundation, J.D.A. was supported by an American Cancer Society postdoctoral fellowship, J.J.B. was supported by a National Institute of Health training grant (AI 19512) and by a fellowship from the Irvington Institute for Medical Research, and D.S.L. is supported by a Howard Hughes Medical Institute predoctoral fellowship. Funding for this work was from the Howard Hughes Medical Institute.
Funders:
Funding AgencyGrant Number
Rothschild FoundationUNSPECIFIED
American Cancer SocietyUNSPECIFIED
NIHAI 19512
Irvington Institute for Medical ResearchUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:6
PubMed Central ID:PMC20116
Record Number:CaltechAUTHORS:20141203-100719213
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141203-100719213
Official Citation:Reich, Z., Altman, J. D., Boniface, J. J., Lyons, D. S., Kozono, H., Ogg, G., . . . Davis, M. M. (1997). Stability of empty and peptide-loaded class II major histocompatibility complex molecules at neutral and endosomal pH: Comparison to class I proteins. Proceedings of the National Academy of Sciences, 94(6), 2495-2500.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52318
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:03 Dec 2014 20:14
Last Modified:03 Oct 2019 07:41

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