Donut-shaped fingerprint in homologous polypeptide relationships--a topological feature related to pathogenic structural changes in conformational disease.
Donut-shaped fingerprint in homologous polypeptide relationships--a topological feature related to pathogenic structural changes in conformational disease.
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同源多肽关系中的甜甜圈形指纹 - 与构象疾病的致病结构变化有关的拓扑特征。
DOI：
10.1016/j.jtbi.2009.02.009
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发表时间：
2009-05-21
影响因子：
2
通讯作者：
Zhao YP
中科院分区：
文献类型：
--
作者：
Liu X;Zhao YP
蛋白质同源关系的特征可以为我们提供蛋白质宇宙的总体图景，有助于蛋白质的设计和分析，并进一步加深我们对生物进化的理解。在这里，我们通过研究残基片段之间的同源关系来研究蛋白质分子的进化。目的是确定整个蛋白质宇宙中短残基片段的同源关系的详细拓扑特征。在大量非冗余蛋白数据的基础上，从残基突变和结构保守两方面对非膜多肽进行了分析。通过将同源片段与边连接，得到了整个短残段的同源关系网络，我们将其命名为多肽关系图（GPR）。由于网络拓扑转换极其复杂，为了获得更深入的理解，我们只分析由探地雷达重要节点组成的子图。这种对探地雷达重要子图的分析揭示了一个甜甜圈形状的指纹。利用这一拓扑特征揭示了正常富-螺旋朊蛋白向富-薄片朊蛋白的构象转换的开关位点（在这里开始暴露先前隐藏的原纤维形成的“热点”，因此提供了进一步的蛋白质聚集机会；188-202），这被认为是导致一组致命的神经退行性疾病，传染性海绵状脑病的原因。还介绍了在分析与各种构象疾病相关的其他蛋白质方面所做的努力。
Features of homologous relationship of proteins can provide us a general picture of protein universe, assist protein design and analysis, and further our comprehension of the evolution of organisms. Here we carried out a study of the evolution of protein molecules by investigating homologous relationships among residue segments. The motive was to identify detailed topological features of homologous relationships for short residue segments in the whole protein universe. Based on the data of a large number of non-redundant proteins, the universe of non-membrane polypeptide was analyzed by considering both residue mutations and structural conservation. By connecting homologous segments with edges, we obtained a homologous relationship network of the whole universe of short residue segments, which we named the graph of polypeptide relationships (GPR). Since the network is extremely complicated for topological transitions, to obtain an in-depth understanding, only subgraphs composed of vital nodes of the GPR were analyzed. Such analysis of vital subgraphs of the GPR revealed a donut-shaped fingerprint. Utilization of this topological feature revealed the switch sites (where the beginning of exposure of previously hidden “hot spots” of fibril-forming happens, in consequence a further opportunity for protein aggregation is provided; 188–202) of the conformational conversion of the normal -helix-rich prion protein to the -sheet-rich that is thought to be responsible for a group of fatal neurodegenerative diseases, transmissible spongiform encephalopathies. Efforts in analyzing other proteins related to various conformational diseases are also introduced.
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影响因子：
4.1
作者：
CHOU, KC;FORSEN, S
通讯作者：
FORSEN, S
影响因子：
14.8
作者：
Chou, Kuo-Chen;Shen, Hong-Bin
通讯作者：
Shen, Hong-Bin
影响因子：
13.8
作者：
Dobson, CM
通讯作者：
Dobson, CM
DOI：
10.1073/pnas.96.6.2591
发表时间：
1999-03-16
影响因子：
11.1
作者：
Bogarad, LD;Deem, MW
通讯作者：
Deem, MW
人类细胞信号网络的社区结构。
影响因子：
2
作者：
Diao Y;Li M;Feng Z;Yin J;Pan Y
通讯作者：
Pan Y