An analysis of protein domain linkers: their classification and role in protein folding

An analysis of protein domain linkers: their classification and role in protein folding
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DOI:
10.1093/protein/15.11.871
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发表时间:
2002-11-01
期刊:
PROTEIN ENGINEERING
影响因子:
--
通讯作者:
Heringa, J
Heringa, J
中科院分区:
其他
文献类型:
--
作者:
George, RA;Heringa, J

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蛋白质工程的最新进展来自于创建包含各种蛋白质模块的多功能嵌合蛋白质。这些模块通常通过寡肽接头连接,其正确设计对于嵌合蛋白的所需功能至关重要。在这里,我们分析自然存在的域间链接器的属性,旨在设计用于域融合的链接器。确定了两种主要类型的接头;螺旋和非螺旋。螺旋接头被认为充当分隔两个域的刚性间隔物。非螺旋接头丰富。脯氨酸,这也导致结构刚性以及连接子与连接域的隔离。这意味着两种接头类型都可能充当支架,以防止折叠域之间的不利相互作用。基于这些结果,我们构建了一个链接数据库,用于合理设计域融合链接,可以通过互联网访问:http://mathbio.nimr.mrc.ac.uk。
Recent advances in protein engineering have come from creating multi-functional chimeric proteins containing modules from various proteins. These modules are typically joined via an oligopeptide linker, the correct design of which is crucial for the desired function of the chimeric protein. Here we analyse the properties of naturally occurring inter-domain linkers with the aim to design linkers for domain fusion. Two main types of linker were identified; helical and non-helical. Helical linkers are thought to act as rigid spacers separating two domains. Non-helical linkers are rich. in prolines, which also leads to structural rigidity and isolation of the linker from the attached domains. This means that both linker types are likely to act as a scaffold to prevent unfavourable interactions between folding domains. Based on these results we have constructed a linker database intended for the rational design of linkers for domain fusion, which can be accessed via the Internet at http://mathbio.nimr.mrc.ac.uk.