当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Molecular flexibility can influence the stimulatory ability of receptor-ligand interactions at cell-cell junctions.

Molecular flexibility can influence the stimulatory ability of receptor-ligand interactions at cell-cell junctions.

Abstract：

:Direct cell-cell communication is crucial for many processes in biology, particularly embryogenesis, interactions between hematopoetic cells, and in the nervous system. This communication is often mediated by the binding of receptors to cognate ligands at a cell-cell junction. One such interaction that is very important for the development of many immune responses is the binding of the alphabeta T cell receptor for antigen (TCR) on T lymphocytes with peptide-MHC complexes on other cells. In general, the stability (e.g., half-life) of TCR-peptide-MHC binding measured in solution correlates with functional responses. Several anomalies have been reported, however. For example, for some anomalous ligands, large changes in heat capacity can apparently substitute for a lack of stability in TCR-ligand interactions. Here, we show that, when there are significant conformational changes during receptor-ligand binding and the receptor/ligand have relatively rigid molecular subdomains, the difference between the half-life of this receptor-ligand complex at a cell-cell junction and that measured using soluble molecules is large. Thus, receptors/ligands with these specific molecular features do not follow correlations between stimulatory potency in the cellular environment and half-lives measured with soluble molecules. Our "first-principles" prescription for correcting the half-life measured in solution to obtain the pertinent value at a cell-cell junction illuminates the origin of correlations of T cell response with thermodynamic properties. Application of our ideas to diverse systems where receptor-ligand interactions occur across juxtaposed cells may help avoid debates about "anomalies" that may simply arise from receptor/ligand-specific differences between half-lives in solution and in the cellular environment.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Qi S,Krogsgaard M,Davis MM,Chakraborty AK

doi

10.1073/pnas.0510991103

keywords:

subject

Has Abstract

pub_date

2006-03-21 00:00:00

pages

4416-21

issue

eissn

0027-8424

issn

1091-6490

pii

0510991103

journal_volume

103

pub_type

杂志文章

在线工具

Molecular flexibility can influence the stimulatory ability of receptor-ligand interactions at cell-cell junctions.