麻省理工大学：《Systems Biology》Fine tuned model for perfect adaptation

Fine tuned model for perfect adaptation spiro et a1.PNAs94,7263-7268(1997) A model of excitation and adaptation in bacterial chemotaxis

‘Fine tuned model for perfect adaptation’ Spiro et al. PNAS 94, 7263-7268 (1997) A model of excitation and adaptation in bacterial chemotaxis

+ATT flagellar +cH3-8 motor MCPs MCPs CW PA--CHa ATP ATP ADP Z B (YP, Figure 1 of Spiro, P. A, J.S. Parkinson, and H. G. Othmer A model of excitation and adaptation in bacterial chemotaxis Proc Nat/ Acad SciU sA 94, no 14 Jul 8, 1997):7263-8 Copyright (1997) National Academy of Sciences, U.S.A key player: Tar-CheA-CheW complex

key player: Tar-CheA-CheW complex Copyright (1997) National Academy of Sciences, U. S. A. Figure 1 of Spiro, P. A., J. S. Parkinson, and H. G. Othmer. Proc Natl Acad Sci U S A 94, no. 14 (Jul 8, 1997): 7263-8. "A model of excitation and adaptation in bacterial chemotaxis

assumptions 1. Tar is only receptor type, chew and cheA a lways bound to tar 2. Methylation occurs in specific order 3. Consider only 3 highest methylation states 4. Only cheB demethylate 5. Phoshorylation of chea does not affect ligand (un)binding 6. Tar-cher binding does not affect ligand un (binding) and phosphorylation of cheA Chez is not regulated 8. Phosphotransfer from complex to CheY or Cheb is not affected by occupancy or methylation state

assumptions: 1. Tar is only receptor type, CheW and CheA always bound to Tar 2. Methylation occurs in specific order 3. Consider only 3 highest methylation states 4. Only CheBp demethylates 5. Phoshorylation of CheA does not affect ligand (un)binding 6. Tar-CheR binding does not affect ligand un(binding) and phosphorylation of CheA 7. CheZ is not regulated 8. Phosphotransfer from complex to CheY or CheB is not affected by occupancy or methylation state

Phosphorylation Methylation gand e Binding七e ,+SlowT34-T fast A Y B B Figure 2 of Spiro, P. A, J.S. Parkinson, and H. G. Othmer A model of excitation and adaptation in bacterial chemotaxis Proc Nat/ Acad SciUSA 94, no 14 (Jul 8, 1997): 7263-8

fast slow intermediate Copyright (1997) National Academy of Sciences, U. S. A. Figure 2 of Spiro, P. A., J. S. Parkinson, and H. G. Othmer. Proc Natl Acad Sci U S A 94, no. 14 (Jul 8, 1997): 7263-8. "A model of excitation and adaptation in bacterial chemotaxis

Ligand bound states generally have lower autophosphorylation rates Phosphorylation Methylation igan Binding 4p 2 p -LI 3p 3 Figure 2 of Spiro, P. A, J S Parkinson, and H. G Othmer A model of excitation and adaptation in bacterial chemotaxis Proc Nat/ Acad Sci UsA94, no 14(Jul 8, 1997): 7263-8

Ligand bound states generally have lower autophosphoryalation rates Copyright (1997) National Academy of Sciences, U. S. A. Copyright (1997) National Academy of Sciences, U. S. A. Figure 2 of Spiro, P. A., J. S. Parkinson, and H. G. Othmer. Proc Natl Acad Sci U S A 94, no. 14 (Jul 8, 1997): 7263-8. "A model of excitation and adaptation in bacterial chemotaxis

Cher methylates ligand-bound states more rapidly Phosphorvlation Methylation Ligand Binding p 4p 3 A LT 3p p 2 3 Figure 2 of Spiro, P. A, J.S. Parkinson, and H. G. Othmer A model of excitation and adaptation in bacterial chemotaxis. "Proc Nat/ Acad SciUSA94, no. 14 Jul 8, 1997): 7263-8 Copyright (1997) National Academy of Sciences, U.S.A

CheR methylates ligand-bound states more rapidly Copyright (1997) National Academy of Sciences, U. S. A. Figure 2 of Spiro, P. A., J. S. Parkinson, and H. G. Othmer. "A model of excitation and adaptation in bacterial chemotaxis." Proc Natl Acad Sci U S A 94, no. 14 (Jul 8, 1997): 7263-8

Consider step in aspartate concentration time w 1 ms, increase in ligand bound complex Phosphorylation Methylation gand 3p T Binding →"T3 LT 3p ·L14p LT Figure 2 of Spiro, P. A, J.S. Parkinson, and H. G. Othmer A model of excitation and adaptation in bacterial chemotaxis. Proc Nat/ Acad SciUsA94, no. 14 Jul 8, 1997): 7263-8 Copyright (1997) National Academy of Sciences, U.S. A

Consider step in aspartate concentration time ~ 1 ms, increase in ligand bound complex Copyright (1997) National Academy of Sciences, U. S. A. Figure 2 of Spiro, P. A., J. S. Parkinson, and H. G. Othmer. "A model of excitation and adaptation in bacterial chemotaxis." Proc Natl Acad Sci U S A 94, no. 14 (Jul 8, 1997): 7263-8

time w 5 s, total of phosphorylated complexes decreases gradually because ligand bound complexes do not autophoshorylate very well Phosphorylation also: cheb decreases Methylation low CheA, low chey tumble suppression Ligand p T Binding →T2 p 3p LT Figure 2 of Spiro, P. A, J.S. Parkinson, and H. G. Othmer A model of excitation and adaptation in bacterial chemotaxis. Proc Natl Acad Sci U SA94, no. 14(Jul 8, 1997 ): 7263-8 Copyright(1997) National Academy of Sciences, U.S.A

time ~ 5 s, total # of phosphorylated complexes decreases gradually because ligand bound complexes do not autophoshorylate very well also: CheB p decreases low CheA p, low CheY p, tumble suppression Copyright (1997) National Academy of Sciences, U. S. A. Figure 2 of Spiro, P. A., J. S. Parkinson, and H. G. Othmer. "A model of excitation and adaptation in bacterial chemotaxis." Proc Natl Acad Sci U S A 94, no. 14 (Jul 8, 1997): 7263-8

time w 50 s, slowly the complex methylates Note that demethylation is switched off because of low levels of chea (low CheB Phosphorylation also low CheA low CheY p tumble suppression Methylation Liga 罗3p T Binding LT 3p LTAP Figure 4 of Spiro, P. A, J.S. Parkinson, and H. G. Othmer A model of excitation and adaptation in bacterial chemotaxis. Proc Nat/ Acad Sci SA94, no. 14 (Jul 8, 1997): 7263-8 Copyright ( 1997) National academy of sciences, U.s.a

time ~ 50 s, slowly the complex methylates. Note that demethylation is switched off because of low levels of CheA p (low CheB p). also low CheA p, low CheY p, tumble suppression Copyright (1997) National Academy of Sciences, U. S. A. Figure 4 of Spiro, P. A., J. S. Parkinson, and H. G. Othmer. "A model of excitation and adaptation in bacterial chemotaxis." Proc Natl Acad Sci U S A 94, no. 14 (Jul 8, 1997): 7263-8

Higher methylation states autophosphorylate easier, so slowly CheA adapts to its initial level Phosphorylation high CheA high CheY p tumblin Methylation Ligand Binding 3p 4p T LT 2p LT LT Figure 4 of Spiro, P. A, J.S. Parkinson, and H. G. Othmer A model of excitation and adaptation in bacterial chemotaxis. Proc Natl Acad SciU S A 94, no. 14(Jul 8, 1997): 7263-8 Copyright(1997) National Academy of Sciences, U.S.A

Higher methylation states autophosphorylate easier, so slowly CheA p adapts to its initial level high CheA p, high CheY p, tumbling Copyright (1997) National Academy of Sciences, U. S. A. Figure 4 of Spiro, P. A., J. S. Parkinson, and H. G. Othmer. "A model of excitation and adaptation in bacterial chemotaxis." Proc Natl Acad Sci U S A 94, no. 14 (Jul 8, 1997): 7263-8