Ligand detection and discrimination by spatial relocalization: A kinase-phosphatase segregation model of TCR activation.


:We develop a model of tyrosine phosphorylation and activation of the T-cell receptor (TCR) by localization to regions of close membrane-membrane proximity (close contact) that physically exclude tyrosine phosphatases such as CD45. Phosphatase exclusion generates regions of low phosphatase and high kinase activity and thus our model provides a framework to examine the kinetic segregation model of TCR activation. We incorporate a sequence of activation steps modeling the construction of the signalosome with a final sequestered, or high-stability, signaling state. The residence time of unbound TCRs in tyrosine kinase-rich domains is shown to be too short for accumulation of activation steps, whereas binding to an agonist lengthens the localization time and leads to generation of fully active TCRs. Agonist detection depends only on this localization, and therefore kinetic segregation represents a viable ligand detection mechanism, or signal transduction mechanism across membranes, distinct from receptor oligomerization and conformational change. We examine the degree of discrimination of agonists from a background of null (self) peptides, and from weak agonists achievable by this mechanism.


Biophys J


Biophysical journal


Burroughs NJ,Lazic Z,van der Merwe PA




Has Abstract


2006-09-01 00:00:00














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    abstract::As normally studied, in the solid state or in solution, poly(beta-benzyl-L-aspartate) (PBLA) differs from the other helical polyamino acids in that its alpha-helical conformation is most stable in the left-handed rather than in the right-handed form. The slightly lower energy per residue for the left-handed form in PB...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Riou SA,Hsu SL,Stidham HD

    更新日期:1998-11-01 00:00:00

  • A slow component of gating current in crayfish giant axons resembles inactivation charge movement.

    abstract::Recent experimental evidence from a number of preparations indicates that sodium channel inactivation may be intrinsically voltage sensitive. Intrinsically voltage sensitive inactivation should produce a charge movement. Crayfish giant axons provide a unique opportunity to reexamine the slower components of gating cur...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Swenson RP Jr

    更新日期:1983-03-01 00:00:00

  • Diffusion coefficient of the cyclic GMP analog 8-(fluoresceinyl)thioguanosine 3',5' cyclic monophosphate in the salamander rod outer segment.

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Koutalos Y,Brown RL,Karpen JW,Yau KW

    更新日期:1995-11-01 00:00:00

  • Time-resolved absorption and magnetic circular dichroism spectroscopy of cytochrome c3 from Desulfovibrio.

    abstract::The UV-visible absorption and magnetic circular dichroism (MCD) spectra of the ferric, ferrous, CO-ligated forms and kinetic photolysis intermediates of the tetraheme electron-transfer protein cytochrome c3 (Cc3) are reported. Consistent with bis-histidinyl axial coordination of the hemes in this Class III c-type cyto...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: O'Connor DB,Goldbeck RA,Hazzard JH,Kliger DS,Cusanovich MA

    更新日期:1993-10-01 00:00:00

  • Digitized precision measurements of the movements of sea urchin sperm flagella.

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Rikmenspoel R,Isles CA

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  • Searching the Optimal Folding Routes of a Complex Lasso Protein.

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Perego C,Potestio R

    更新日期:2019-07-23 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Blasie JK

    更新日期:1972-02-01 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Cimmperman P,Baranauskiene L,Jachimoviciūte S,Jachno J,Torresan J,Michailoviene V,Matuliene J,Sereikaite J,Bumelis V,Matulis D

    更新日期:2008-10-01 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Farinas J,Verkman AS

    更新日期:1996-12-01 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Sullivan DC,Kuntz ID

    更新日期:2004-07-01 00:00:00

  • Electric field-induced changes in lipids investigated by modulated excitation FTIR spectroscopy.

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Schwarzott M,Lasch P,Baurecht D,Naumann D,Fringeli UP

    更新日期:2004-01-01 00:00:00

  • Order in phospholipid Langmuir-Blodgett monolayers determined by total internal reflection fluorescence.

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Zhai X,Kleijn JM

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Lucas MF,Guallar V

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Sugiyama T,Miyashiro D,Takao D,Iwamoto H,Sugimoto Y,Wakabayashi K,Kamimura S

    更新日期:2009-12-16 00:00:00

  • Gold-nanoparticle-assisted laser perturbation of chromatin assembly reveals unusual aspects of nuclear architecture within living cells.

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Mazumder A,Shivashankar GV

    更新日期:2007-09-15 00:00:00

  • Change of motion and localization of cholesterol molecule during L(alpha)-H(II) transition.

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Hayakawa E,Naganuma M,Mukasa K,Shimozawa T,Araiso T

    更新日期:1998-02-01 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Miao Y,Caliman AD,McCammon JA

    更新日期:2015-04-07 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Derreumaux S,Fermandjian S

    更新日期:2000-08-01 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Gorham RD Jr,Rodriguez W,Morikis D

    更新日期:2014-03-04 00:00:00

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    abstract::This study presents a simplified version of the quasi-one-dimensional theory (Wu, J., E. A. Johnson, and J. M. Kootsey. 1996. A quasi-one-dimensional theory for anisotropic propagation of excitation in cardiac muscle. Biophys. J. 71:2427-2439) with two components of the extracellular current, along and perpendicular t...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Wu J,Wikswo JP Jr

    更新日期:1997-11-01 00:00:00

  • Vibrational neutron spectroscopy of collagen and model polypeptides.

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Middendorf HD,Hayward RL,Parker SF,Bradshaw J,Miller A

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    abstract::Most, but not all, ion channels appear to obey the law of microscopic reversibility (or detailed balance). During the fitting of reaction mechanisms it is therefore often required that cycles in the mechanism should obey microscopic reversibility at all times. In complex reaction mechanisms, especially those that cont...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Colquhoun D,Dowsland KA,Beato M,Plested AJ

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    pub_type: 杂志文章


    authors: Barros EP,Casalino L,Gaieb Z,Dommer AC,Wang Y,Fallon L,Raguette L,Belfon K,Simmerling C,Amaro RE

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Miller RN,Rinzel J

    更新日期:1981-05-01 00:00:00

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    abstract::Titin is a giant filamentous polypeptide of multidomain construction spanning between the Z- and M-lines of the cardiac muscle sarcomere. Extension of the I-band segment of titin gives rise to a force that underlies part of the diastolic force of cardiac muscle. Titin's force arises from its extensible I-band region, ...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Trombitás K,Freiburg A,Centner T,Labeit S,Granzier H

    更新日期:1999-12-01 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Sergeev M,Costantino S,Wiseman PW

    更新日期:2006-11-15 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Alexov EG,Gunner MR

    更新日期:1997-05-01 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Gensler W

    更新日期:1979-09-01 00:00:00

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    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Condat CA,Jäckle J

    更新日期:1989-05-01 00:00:00

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    abstract::A comparative analysis of two models of anisotropic reactivity in bimolecular diffusion-controlled reaction kinetics is presented. One is the conventional model of reactive patches (MRP), where the surface of a molecule is assumed to be reactive over a certain region (circular patch) with the rest of the surface being...

    journal_title:Biophysical journal

    pub_type: 杂志文章


    authors: Barzykin AV,Shushin AI

    更新日期:2001-05-01 00:00:00