Markov propagation of allosteric effects in biomolecular systems: application to GroEL-GroES.
Markov propagation of allosteric effects in biomolecular systems: application to GroEL-GroES.
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DOI：
10.1038/msb4100075
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发表时间：
2006
影响因子：
9.9
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中科院分区：
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我们介绍了一种新的方法来阐明生物分子系统中的变构通讯的潜在途径。该方法，基于马尔可夫传播的“信息”的结构，使我们能够划分网络的相互作用成软集群区分其连贯的随机。残基在这些集群中的可能参与定义了网络架构所固有的通信模式。应用于细菌伴侣蛋白复合物GroEL-GroES，一种变构驱动的结构，鉴定了参与亚基内和亚基间通信的残基，包括充当枢纽和信使的残基。许多残基的区别在于它们传递变构信号的高潜力，包括核苷酸结合位点处的Pro 33和Thr 90以及分别介导环间和环内通信的Glu 461和Arg 197。我们提出了两个最有可能的信号传输途径，核苷酸和GroES结合位点之间的顺式和反式环，其中涉及几个保守的残基。一个引人注目的观察是顺式和反式环内信息流的相反方向，与负环间协同性一致。从正常模式分析推导出的集体模式的比较揭示了全球铰链区的倾向，作为信使在传输变构信号。
We introduce a novel approach for elucidating the potential pathways of allosteric communication in biomolecular systems. The methodology, based on Markov propagation of ‘information' across the structure, permits us to partition the network of interactions into soft clusters distinguished by their coherent stochastics. Probabilistic participation of residues in these clusters defines the communication patterns inherent to the network architecture. Application to bacterial chaperonin complex GroEL–GroES, an allostery-driven structure, identifies residues engaged in intra- and inter-subunit communication, including those acting as hubs and messengers. A number of residues are distinguished by their high potentials to transmit allosteric signals, including Pro33 and Thr90 at the nucleotide-binding site and Glu461 and Arg197 mediating inter- and intra-ring communication, respectively. We propose two most likely pathways of signal transmission, between nucleotide- and GroES-binding sites across the cis and trans rings, which involve several conserved residues. A striking observation is the opposite direction of information flow within cis and trans rings, consistent with negative inter-ring cooperativity. Comparison with collective modes deduced from normal mode analysis reveals the propensity of global hinge regions to act as messengers in the transmission of allosteric signals.