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Peptide Interaction with a Class I Major Histocompatibility Complex-Encoded Molecule: Allosteric Control of the Ternary Complex Stability

Gakamsky, Dmitry M. and Bjorkman, Pamela J. and Pecht, Israel (1996) Peptide Interaction with a Class I Major Histocompatibility Complex-Encoded Molecule: Allosteric Control of the Ternary Complex Stability. Biochemistry, 35 (47). pp. 14841-14848. ISSN 0006-2960. http://resolver.caltech.edu/CaltechAUTHORS:20170406-080910653

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Abstract

Thermodynamics and kinetics of interaction between a soluble class I MHC heterodimer composed of the H-2K^d heavy chain (H) and human β_2 microglobulin (β_2m) with a dansylated peptide series based on residues 147−155 of influenza virus nucleoprotein sequence were studied by means of real-time fluorescence measurements. Peptide−heterodimer binding is a second-order process with specific rates practically independent of peptide structure (3−5 × 10^6 M^(-1) s^(-1)). The ternary complex assembly involves a rate-limiting step of β_2m association with H to yield an unstable heterodimer (τ ≤ 5 s, 37 °C). Peptide binding provides a positive feedback enhancing H's affinity for β_2m, thus stabilizing the ternary complex. The latter decays by either peptide or β2m dissociation. The first-order rate constants of peptide dissociation ((0.5 × 10^(-2))−(0.4 × 10^(-3)) s^(-1), 37 °C) depend on their structures and are faster than that of β_2m dissociation. The former process decreases the H affinity for β_2m and induces their dissociation. This dissociation, in turn, drastically lowers H affinity for peptide. Thus, these three components produce a system which is stable as a trimer. This behavior is rationalized by the functional requirements of class I molecules:  Peptide structure determines the ternary complex's lifetime, and peptide rebinding on the cell surface is rendered unlikely by the limited stability of the empty heterodimers and the very low peptide affinity of the heavy chains.


Item Type:Article
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http://dx.doi.org/10.1021/bi961707uDOIArticle
http://pubs.acs.org/doi/abs/10.1021/bi961707uPublisherArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 1996 American Chemical Society. Received July 12, 1996; Revised Manuscript Received September 12, 1996. Publication Date (Web): November 26, 1996. This study is part of a collaborative Lower Saxony-Israeli Research Project supported by a grant provided by the Ministry for Science and Culture of Lower Saxony, FRG. We thank Ms. J. Johnson for production and purification of the recombinant H-2Kd molecules, Dr. Y. Shai for HPLC peptide purification, and Mr. A. Licht for technical assistance. We are greatly indebted to Dr. A. A. Goldin for generously providing the Global Analysis program.
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Ministry for Science and Culture (Lower Saxony)UNSPECIFIED
Record Number:CaltechAUTHORS:20170406-080910653
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20170406-080910653
Official Citation:Peptide Interaction with a Class I Major Histocompatibility Complex-Encoded Molecule:  Allosteric Control of the Ternary Complex Stability Dmitry M. Gakamsky, Pamela J. Bjorkman, and Israel Pecht Biochemistry 1996 35 (47), 14841-14848 DOI: 10.1021/bi961707u
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:75781
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:06 Apr 2017 15:49
Last Modified:06 Apr 2017 15:49

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