A free-energy-based stochastic simulation of the Tar receptor complex

被引:96
作者
Morton-Firth, CJ [1 ]
Shimizu, TS [1 ]
Bray, D [1 ]
机构
[1] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England
基金
英国医学研究理事会;
关键词
bacterial chemotaxis; signalling complex; conformational change; free-energy; individual-based modelling;
D O I
10.1006/jmbi.1999.2535
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We recently developed a stochastic-based program that allows individual molecules in a cell signalling pathway to be simulated. This program has now been used to model the Tar complex, a multimeric signalling complex employed by coliform bacteria. This complex acts as a solid-state computational cassette, integrating and disseminating information on the presence of attractants and repellents in the environment of the bacterium. In our model, the Tar complex exists in one of two conformations which differ in the rate at which they generate labile phosphate groups and hence signal to the flagellar motor. Individual inputs to the complex (aspartate binding, methylation at different sites, binding of CheB, CheR and CheY) are represented as binary flags, and each combination of nags confers a different free energy to the two conformations. Binding and catalysis by the complex are performed stochastically according to the complete set of known reactions allowing the swimming performance of the bacterium to be predicted. The assumption of two conformational states together with the use of free energy values allows us to bring together seemingly unrelated experimental parameters. Because of thermodynamic constraints, we find that the binding affinity for aspartate is linked to changes in phosphorylation activity. We estimate the pattern of Tar methylation and effective affinity constant of receptors over a range of aspartate levels. We also obtain evidence that both the methylating and demethylating enzymes must operate exclusively on one or other of the two conformations, and that sites of methylation of the complex are occupied in sequential order rather than independently. Detailed analysis of the response to aspartate reveals several quantitative discrepancies between simulated and experimental data which indicate areas for future research. (C) 1999 Academic Press.
引用
收藏
页码:1059 / 1074
页数:16
相关论文
共 54 条
[1]   Response regulator output in bacterial chemotaxis [J].
Alon, U ;
Camarena, L ;
Surette, MG ;
Arcas, BAY ;
Liu, Y ;
Leibler, S ;
Stock, JB .
EMBO JOURNAL, 1998, 17 (15) :4238-4248
[2]   2-STATE MODEL FOR BACTERIAL CHEMORECEPTOR PROTEINS - THE ROLE OF MULTIPLE METHYLATION [J].
ASAKURA, S ;
HONDA, H .
JOURNAL OF MOLECULAR BIOLOGY, 1984, 176 (03) :349-367
[3]   Robustness in simple biochemical networks [J].
Barkai, N ;
Leibler, S .
NATURE, 1997, 387 (6636) :913-917
[4]   TRANSIENT-RESPONSE TO CHEMOTACTIC STIMULI IN ESCHERICHIA-COLI [J].
BERG, HC ;
TEDESCO, PM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1975, 72 (08) :3235-3239
[5]   ASPARTATE RECEPTORS OF ESCHERICHIA-COLI AND SALMONELLA-TYPHIMURIUM BIND LIGAND WITH NEGATIVE AND HALF-OF-THE-SITES COOPERATIVITY [J].
BIEMANN, HP ;
KOSHLAND, DE .
BIOCHEMISTRY, 1994, 33 (03) :629-634
[6]   DEMETHYLATION OF BACTERIAL CHEMORECEPTORS IS INHIBITED BY ATTRACTANT STIMULI IN THE COMPLETE ABSENCE OF THE REGULATORY DOMAIN OF THE DEMETHYLATING ENZYME [J].
BORCZUK, A ;
STAUB, A ;
STOCK, J .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 141 (03) :918-923
[7]   ATTENUATION OF SENSORY RECEPTOR SIGNALING BY COVALENT MODIFICATION [J].
BORKOVICH, KA ;
ALEX, LA ;
SIMON, MI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (15) :6756-6760
[8]   TRANSMEMBRANE SIGNAL TRANSDUCTION IN BACTERIAL CHEMOTAXIS INVOLVES LIGAND-DEPENDENT ACTIVATION OF PHOSPHATE GROUP TRANSFER [J].
BORKOVICH, KA ;
KAPLAN, N ;
HESS, JF ;
SIMON, MI .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (04) :1208-1212
[9]   THE DYNAMICS OF PROTEIN-PHOSPHORYLATION IN BACTERIAL CHEMOTAXIS [J].
BORKOVICH, KA ;
SIMON, MI .
CELL, 1990, 63 (06) :1339-1348
[10]   SIGNAL TRANSDUCTION PATHWAYS INVOLVING PROTEIN-PHOSPHORYLATION IN PROKARYOTES [J].
BOURRET, RB ;
BORKOVICH, KA ;
SIMON, MI .
ANNUAL REVIEW OF BIOCHEMISTRY, 1991, 60 :401-441