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转导素GTP酶循环的随机模拟。

Stochastic simulation of the transducin GTPase cycle.

作者信息

Felber S, Breuer H P, Petruccione F, Honerkamp J, Hofmann K P

机构信息

Institut für Medizinische Physik und Biophysik, Medizinische Fakultät Charité, Humboldt-Universität zu Berlin, Germany.

出版信息

Biophys J. 1996 Dec;71(6):3051-63. doi: 10.1016/S0006-3495(96)79499-7.

DOI:10.1016/S0006-3495(96)79499-7
PMID:8968576
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1233794/
Abstract

On rod disc membranes, single photoactivated rhodopsin (R*) molecules catalytically activate many copies of the G-protein (Gt), which in turn binds and activates the effector (phosphodiesterase). We have performed master equation simulations of the underlying diffusional protein interactions on a rectangular 1-micron2 model membrane, divided into 15 x 15 cells. Mono- and bimolecular reactions occur within cells, and diffusional transitions occur between (neighboring) cells. Reaction and diffusion constants yield the related probabilities for the stochastic transitions. The calculated kinetics of active effector form a response that is essentially determined by the stochastic lifetime distribution of R* (with characteristic time tau R*) and the reaction constants of Gt activation. Only a short tau R* (approximately 0.3 s) and a high catalytic rate (3000-4000 Gt s-1 R*-1) are consistent with electrophysiological data. Although R* shut-off limits the rise of the response, the lifetime distribution of free R* is not translated into a corresponding variability of the response peaks, because 1) the lifetime distribution of catalytically engaged R* is distorted, 2) small responses are enlarged by an overshoot of active effector, and 3) larger responses tend to undergo saturation. Comparison of these results to published photocurrent waveforms may open ways to understand the relative uniformity of the rod response.

摘要

在视杆盘膜上,单个光激活的视紫红质(R*)分子催化激活许多拷贝的G蛋白(Gt),而G蛋白又结合并激活效应器(磷酸二酯酶)。我们在一个1平方微米的矩形模型膜上进行了主方程模拟,该膜被划分为15×15个单元格,模拟了潜在的扩散性蛋白质相互作用。单分子和双分子反应在单元格内发生,扩散性转变在(相邻的)单元格之间发生。反应和扩散常数产生了随机转变的相关概率。计算得到的活性效应器的动力学形成了一种响应,该响应基本上由R的随机寿命分布(特征时间为tau R)和Gt激活的反应常数决定。只有较短的tau R*(约0.3秒)和较高的催化速率(3000 - 4000 Gt s-1 R*-1)与电生理数据一致。尽管R的失活限制了响应的上升,但游离R的寿命分布并没有转化为响应峰值的相应变化,原因如下:1)催化参与的R*的寿命分布发生了扭曲;2)小响应因活性效应器的过冲而放大;3)大响应往往会饱和。将这些结果与已发表的光电流波形进行比较,可能为理解视杆细胞响应的相对均匀性开辟道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a0e/1233794/26d368445856/biophysj00042-0147-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a0e/1233794/26d368445856/biophysj00042-0147-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a0e/1233794/26d368445856/biophysj00042-0147-a.jpg

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本文引用的文献

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Responses of the phototransduction cascade to dim light.光转导级联反应对暗光的响应。
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Recovery kinetics of human rod phototransduction inferred from the two-branched alpha-wave saturation function.从双分支α波饱和函数推断的人类视杆光转导恢复动力学
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Multiple steps of phosphorylation of activated rhodopsin can account for the reproducibility of vertebrate rod single-photon responses.活化视紫红质的多步磷酸化可解释脊椎动物视杆单光子反应的可重复性。
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