Distinctive Topologies of Partner-switching Signaling Networks Correlate with their Physiological Roles

Oleg A. Igoshin, Margaret S. Brody, Chester W. Price, Michael A. Savageau

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Regulatory networks controlling bacterial gene expression often evolve from common origins and share homologous proteins and similar network motifs. However, when functioning in different physiological contexts, these motifs may be re-arranged with different topologies that significantly affect network performance. Here we analyze two related signaling networks in the bacterium Bacillus subtilis in order to assess the consequences of their different topologies, with the aim of formulating design principles applicable to other systems. These two networks control the activities of the general stress response factor σB and the first sporulation-specific factor σF. Both networks have at their core a "partner-switching" mechanism, in which an anti-sigma factor forms alternate complexes either with the sigma factor, holding it inactive, or with an anti-anti-sigma factor, thereby freeing sigma. However, clear differences in network structure are apparent: the anti-sigma factor for σF forms a long-lived, "dead-end" complex with its anti-anti-sigma factor and ADP, whereas the genes encoding σB and its network partners lie in a σB-controlled operon, resulting in positive and negative feedback loops. We constructed mathematical models of both networks and examined which features were critical for the performance of each design. The σF model predicts that the self-enhancing formation of the dead-end complex transforms the network into a largely irreversible hysteretic switch; the simulations reported here also demonstrate that hysteresis and slow turn off kinetics are the only two system properties associated with this complex formation. By contrast, the σB model predicts that the positive and negative feedback loops produce graded, reversible behavior with high regulatory capacity and fast response time. Our models demonstrate how alterations in network design result in different system properties that correlate with regulatory demands. These design principles agree with the known or suspected roles of similar networks in diverse bacteria.

Original languageEnglish (US)
Pages (from-to)1333-1352
Number of pages20
JournalJournal of Molecular Biology
Volume369
Issue number5
DOIs
StatePublished - Jun 22 2007

Fingerprint

Sigma Factor
Bacteria
Bacterial Genes
Operon
Bacillus subtilis
Adenosine Diphosphate
Reaction Time
Theoretical Models
Gene Expression
Genes
Proteins

Keywords

  • design
  • feedback
  • sigma factor
  • sporulation
  • stress

ASJC Scopus subject areas

  • Virology

Cite this

Distinctive Topologies of Partner-switching Signaling Networks Correlate with their Physiological Roles. / Igoshin, Oleg A.; Brody, Margaret S.; Price, Chester W.; Savageau, Michael A.

In: Journal of Molecular Biology, Vol. 369, No. 5, 22.06.2007, p. 1333-1352.

Research output: Contribution to journalArticle

Igoshin, Oleg A. ; Brody, Margaret S. ; Price, Chester W. ; Savageau, Michael A. / Distinctive Topologies of Partner-switching Signaling Networks Correlate with their Physiological Roles. In: Journal of Molecular Biology. 2007 ; Vol. 369, No. 5. pp. 1333-1352.
@article{813200bf0b8c46f1b6fba4abee0fae99,
title = "Distinctive Topologies of Partner-switching Signaling Networks Correlate with their Physiological Roles",
abstract = "Regulatory networks controlling bacterial gene expression often evolve from common origins and share homologous proteins and similar network motifs. However, when functioning in different physiological contexts, these motifs may be re-arranged with different topologies that significantly affect network performance. Here we analyze two related signaling networks in the bacterium Bacillus subtilis in order to assess the consequences of their different topologies, with the aim of formulating design principles applicable to other systems. These two networks control the activities of the general stress response factor σB and the first sporulation-specific factor σF. Both networks have at their core a {"}partner-switching{"} mechanism, in which an anti-sigma factor forms alternate complexes either with the sigma factor, holding it inactive, or with an anti-anti-sigma factor, thereby freeing sigma. However, clear differences in network structure are apparent: the anti-sigma factor for σF forms a long-lived, {"}dead-end{"} complex with its anti-anti-sigma factor and ADP, whereas the genes encoding σB and its network partners lie in a σB-controlled operon, resulting in positive and negative feedback loops. We constructed mathematical models of both networks and examined which features were critical for the performance of each design. The σF model predicts that the self-enhancing formation of the dead-end complex transforms the network into a largely irreversible hysteretic switch; the simulations reported here also demonstrate that hysteresis and slow turn off kinetics are the only two system properties associated with this complex formation. By contrast, the σB model predicts that the positive and negative feedback loops produce graded, reversible behavior with high regulatory capacity and fast response time. Our models demonstrate how alterations in network design result in different system properties that correlate with regulatory demands. These design principles agree with the known or suspected roles of similar networks in diverse bacteria.",
keywords = "design, feedback, sigma factor, sporulation, stress",
author = "Igoshin, {Oleg A.} and Brody, {Margaret S.} and Price, {Chester W.} and Savageau, {Michael A.}",
year = "2007",
month = "6",
day = "22",
doi = "10.1016/j.jmb.2007.04.021",
language = "English (US)",
volume = "369",
pages = "1333--1352",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "5",

}

TY - JOUR

T1 - Distinctive Topologies of Partner-switching Signaling Networks Correlate with their Physiological Roles

AU - Igoshin, Oleg A.

AU - Brody, Margaret S.

AU - Price, Chester W.

AU - Savageau, Michael A.

PY - 2007/6/22

Y1 - 2007/6/22

N2 - Regulatory networks controlling bacterial gene expression often evolve from common origins and share homologous proteins and similar network motifs. However, when functioning in different physiological contexts, these motifs may be re-arranged with different topologies that significantly affect network performance. Here we analyze two related signaling networks in the bacterium Bacillus subtilis in order to assess the consequences of their different topologies, with the aim of formulating design principles applicable to other systems. These two networks control the activities of the general stress response factor σB and the first sporulation-specific factor σF. Both networks have at their core a "partner-switching" mechanism, in which an anti-sigma factor forms alternate complexes either with the sigma factor, holding it inactive, or with an anti-anti-sigma factor, thereby freeing sigma. However, clear differences in network structure are apparent: the anti-sigma factor for σF forms a long-lived, "dead-end" complex with its anti-anti-sigma factor and ADP, whereas the genes encoding σB and its network partners lie in a σB-controlled operon, resulting in positive and negative feedback loops. We constructed mathematical models of both networks and examined which features were critical for the performance of each design. The σF model predicts that the self-enhancing formation of the dead-end complex transforms the network into a largely irreversible hysteretic switch; the simulations reported here also demonstrate that hysteresis and slow turn off kinetics are the only two system properties associated with this complex formation. By contrast, the σB model predicts that the positive and negative feedback loops produce graded, reversible behavior with high regulatory capacity and fast response time. Our models demonstrate how alterations in network design result in different system properties that correlate with regulatory demands. These design principles agree with the known or suspected roles of similar networks in diverse bacteria.

AB - Regulatory networks controlling bacterial gene expression often evolve from common origins and share homologous proteins and similar network motifs. However, when functioning in different physiological contexts, these motifs may be re-arranged with different topologies that significantly affect network performance. Here we analyze two related signaling networks in the bacterium Bacillus subtilis in order to assess the consequences of their different topologies, with the aim of formulating design principles applicable to other systems. These two networks control the activities of the general stress response factor σB and the first sporulation-specific factor σF. Both networks have at their core a "partner-switching" mechanism, in which an anti-sigma factor forms alternate complexes either with the sigma factor, holding it inactive, or with an anti-anti-sigma factor, thereby freeing sigma. However, clear differences in network structure are apparent: the anti-sigma factor for σF forms a long-lived, "dead-end" complex with its anti-anti-sigma factor and ADP, whereas the genes encoding σB and its network partners lie in a σB-controlled operon, resulting in positive and negative feedback loops. We constructed mathematical models of both networks and examined which features were critical for the performance of each design. The σF model predicts that the self-enhancing formation of the dead-end complex transforms the network into a largely irreversible hysteretic switch; the simulations reported here also demonstrate that hysteresis and slow turn off kinetics are the only two system properties associated with this complex formation. By contrast, the σB model predicts that the positive and negative feedback loops produce graded, reversible behavior with high regulatory capacity and fast response time. Our models demonstrate how alterations in network design result in different system properties that correlate with regulatory demands. These design principles agree with the known or suspected roles of similar networks in diverse bacteria.

KW - design

KW - feedback

KW - sigma factor

KW - sporulation

KW - stress

UR - http://www.scopus.com/inward/record.url?scp=34248683237&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248683237&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2007.04.021

DO - 10.1016/j.jmb.2007.04.021

M3 - Article

C2 - 17498739

AN - SCOPUS:34248683237

VL - 369

SP - 1333

EP - 1352

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 5

ER -