Kinetics of bimolecular reactions in model bilayers and biological membranes. A critical review

Melo, Eurico; Martins, Jorge

doi:10.1016/j.bpc.2006.05.003

Cited by 45 publications

(52 citation statements)

References 180 publications

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“…This diffusion limit compatible with the Smoluchowski's boundary conditions [21] assumes the zero concentration of quencher, i.e. ground state monomer, in close contact with excited state monomer.…”

Section: Excimer Formation In Rhdlmentioning

confidence: 94%

Cholesteryl ester diffusion, location and self-association constraints determine CETP activity with discoidal HDL: Excimer probe study

Dergunov

Shabrova

Dobretsov

2014

Archives of Biochemistry and Biophysics

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Section: Excimer Formation In Rhdlmentioning

confidence: 94%

Cholesteryl ester diffusion, location and self-association constraints determine CETP activity with discoidal HDL: Excimer probe study

Dergunov

Shabrova

Dobretsov

2014

Archives of Biochemistry and Biophysics

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“…Our observations have novel implications for the biological function of tBID and BCL XL , since they strongly suggest that the most relevant interaction between these proteins, and probably between other homolog proteins of the family, occurs in the membrane, as recently reported for BAX and tBID 4 . Similar membrane-based mechanisms have been proposed in other signaling processes, and indeed this could be a general strategy used by cells to increase interactions between proteins and to modulate downstream cellular responses [49][50][51] . The strong effect of the membrane on tBID/BCL XL complex formation begs other questions, like the role of lipids in the function of the BCL2 proteins, the structures of these proteins in the membrane-bound state or the nature of the interaction surfaces in the lipidic environment.…”

Section: Discussionmentioning

confidence: 99%

Membrane promotes tBID interaction with BCLXL

García‐Sáez

Ries

Orzáez

et al. 2009

Nat Struct Mol Biol

120

141

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SummaryTwo important questions on the molecular mechanism of the BCL2 proteins involve the interaction network between pro-and anti-apoptotic members and the role of their translocation to the mitochondrial membrane during apoptosis. By quantifying the molecular interactions of BID and tBID with BCL XL ΔCt in solution and in membranes by fluorescence correlation spectroscopy, we found that: 1) only the active form tBID binds to BCL XL ΔCt, and 2) the membrane strongly promotes binding between them. Particularly, a BH3 peptide from BID disrupts the tBID/BCL XL complex in solution, but only partially in lipid bilayers. These data indicate that tBID/BCL XL interactions in solution and lipid membranes are distinct, and support a model in which BCL XL inhibition of tBID takes place predominantly at the membrane. Our findings imply an active role of the membrane in modulating the interactions between BCL2 proteins that has been underestimated.

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“…To investigate whether TCR-pMHC rebindings are plausible, we have followed an extensive set of work analyzing diffusioninfluenced reactions (29,30). Our approach has been to apply the particular estimate of the t a , including rebindings, as provided by Bell (31), because of its simplicity and to suggest that the qualitative results are robust to the choice of model (see below and SI Text).…”

Section: Could Rebinding Of Tcrs To Pmhcs Expand the Dwell Time For Fastmentioning

confidence: 99%

Fast on-rates allow short dwell time ligands to activate T cells

Govern¹,

Paczosa

Chakraborty

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

143

167

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Two contrasting theories have emerged that attempt to describe T-cell ligand potency, one based on the t 1/2 of the interaction and the other based on the equilibrium affinity (K D ). Here, we have identified and studied an extensive set of T-cell receptor (TCR)-peptide-MHC (pMHC) interactions for CD4 + cells that have differential K D s and kinetics of binding. Our data indicate that ligands with a short t 1/2 can be highly stimulatory if they have fast onrates. Simple models suggest these fast kinetic ligands are stimulatory because the pMHCs bind and rebind the same TCR several times. Rebinding occurs when the TCR-pMHC on-rate outcompetes TCR-pMHC diffusion within the cell membrane, creating an aggregate t 1/2 (t a ) that can be significantly longer than a single TCRpMHC encounter. Accounting for t a , ligand potency is K D -based when ligands have fast on-rates (k on ) and t 1/2 -dependent when they have slow k on . Thus, TCR-pMHC k on allow high-affinity short t 1/2 ligands to follow a kinetic proofreading model.T cell receptors (TCRs) expressed on T cells bind host MHC proteins presenting both self-and foreign pathogen-derived peptides (pMHCs). Depending on the signal emanating from these interactions, diverse biological outcomes ensue. In the thymus, these TCR-pMHC-mediated signals shape the specificity of the mature T-cell repertoire and prevent overtly self-reactive T cells from escaping (1). In the periphery, naive T cells require continual TCR engagement with self-pMHC complexes to receive a homeostatic survival signal, whereas engagements with foreign peptides induce rapid T-cell division and the acquisition of effector functions (2). How T cells interpret the interaction between their TCR and pMHC ligands leading to these different biological outcomes is greatly debated.Two competing models of T-cell activation have been proposed, with ligand potency being a function of TCR-pMHC equilibrium affinity (K D ) (3-7) or t 1/2 (8-11). Evidence supporting K D -based receptor occupancy models of TCR signaling comes from sets of ligands that show a correlation between the K D and ligand potency (3, 5) and from the fact that ligands induce qualitatively distinct biological outcomes depending on their concentration (12).In sharp contrast to receptor occupancy models, t 1/2 -based kinetic proofreading models hypothesize that the TCR must be engaged long enough to complete a series of signaling events, including coreceptor recruitment and TCR phosphorylation (13). Increases in the t 1/2 of the TCR-pMHC engagement raise the probability that any single TCR-pMHC engagement will surpass the threshold amount of time required to initiate T-cell activation (14). Recently, this threshold amount of time has been predicted to be at least 2 s (9, 15). Whether there is, in addition, an optimal t 1/2 that balances these kinetic proofreading requirements and the serial triggering of TCRs has been debated (16,17).Further evidence supporting t 1/2 -based kinetic proofreading models arises from the discovery of antagonist pMHC l...

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Kinetics of bimolecular reactions in model bilayers and biological membranes. A critical review

Cited by 45 publications

References 180 publications

Cholesteryl ester diffusion, location and self-association constraints determine CETP activity with discoidal HDL: Excimer probe study

Cholesteryl ester diffusion, location and self-association constraints determine CETP activity with discoidal HDL: Excimer probe study

Membrane promotes tBID interaction with BCLXL

Fast on-rates allow short dwell time ligands to activate T cells

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